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  • 1.
    Ghafouri, Bijar
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Irander, Kristina
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Lindbom, John
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Tagesson, Christer
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Lindahl, Mats
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Comparative proteomics of nasal fluid in seasonal allergic rhinitis2006Inngår i: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 5, nr 2, s. 330-338Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A comparative proteomic approach was applied to examine nasal lavage fluid (NLF) from patients with seasonal allergic rhinitis (SAR, n = 6) and healthy subjects (controls, n = 5). NLF samples were taken both before allergy (pollen) season and during season, and proteins were analyzed by two-dimensional gel electrophoresis (2-DE) and matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) after tryptic cleavage. Twenty proteins were selected and quantified. During allergy season, the levels of six sialylated isoforms of PLUNC (palate lung nasal epithelial clone) were lower in SAR patients than controls, as were the levels of six isoforms of von Ebner's gland protein (VEGP), including a previously undescribed form with N-linked glycosylation, and of cystatin S. PLUNC is a new innate immunity protein and VEGP and cystatin S are two endogenous proteinase inhibitors. By contrast, the levels of an acidic form of alpha-1-antitrypsin were higher in SAR patients than controls. One previously unidentified NLF protein was found in all samples from the SAR patients during allergy season but not in any sample before allergy season:  this protein was identified as eosinophil lysophospholipase (Charcot-Leyden crystal protein/galactin 10). MS/MS analysis of the N-terminus of the protein showed removal of Met and acetylation of Ser. Altogether, these findings illustrate the potential use of proteomics for identifying protein changes associated with allergic rhinitis and for revealing post-translational modifications of such new potential markers of allergic inflammation.

  • 2.
    Gustafsson, Mats
    et al.
    Swedish National Road and Transport Research Institute .
    Blomqvist, Göran
    Swedish National Road and Transport Research Institute .
    Gudmundsson, Anders
    Lund University.
    Dahl, Andreas
    Lund University.
    Swietlicki, Erik
    Lund University.
    Bohgard, Mats
    Lund University.
    Lindbom, John
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Ljungman, Anders
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Properties and toxicological effects of particles from the interaction between tyres, road pavement and winter traction material2008Inngår i: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 393, nr 2-3, s. 226-240Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In regions where studded tyres and traction material are used during winter, e.g. the Nordic countries, northern part of USA, Canada, and Japan, mechanically generated particles from traffic is the main reason for high particle concentrations in busy street- and road environments. In many Nordic municipalities the European environmental quality standard for inhalable particles (PM10) is exceeded due to these particles. In this study, particles from the wear of studded and studless friction tyres on two pavements and traction sanding were generated using a road simulator. The particles were characterized using particle sizers, PIXE and electron microscopy. Cell studies were conducted on particles sampled from the tests with studded tyres and compared with street environment, diesel exhaust and subway PM10, respectively. The results show that in the road simulator, where resuspension is minimised, studded tyres produce tens of times more particles than friction tyres. Chemical analysis of the sampled particles shows that the generated wear particles consists almost entirely of minerals from the pavement stone material, but also that S is enriched for the sub-micron particles and that Zn is enriched for friction tyres for all particles sizes. The chemical data can be used for source identification and apportionment in urban aerosol studies. A mode of ultra-fine particles was also present and is hypothesised to originate in the tyres. Further, traction material properties affect PM10 emission. The inflammatory potential of the particles from wear of pavements seems to depend on type of pavement and can be at least as potent as diesel exhaust particles. The results implies that there is a need and a good potential to reduce particle emission from pavement wear and winter time road and street operation by adjusting both studded tyre use as well as pavement and traction material properties.

  • 3.
    Karlsson, Hanna L
    et al.
    Karolinska Institutet, Department of Biosciences and Nutrition at Novum, Unit for Analytical Toxicology, Huddinge, Stockholm, Sweden.
    Ljungman, Anders
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Lindbom, John
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Möller, Lennart
    Karolinska Institutet, Department of Biosciences and Nutrition at Novum, Unit for Analytical Toxicology, Huddinge, Stockholm, Sweden.
    Comparison of genotoxic and inflammatory effects of particles generated by wood combustion, a road simulator and collected from street and subway2006Inngår i: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 165, nr 3, s. 203-211Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The health effects of exposure to airborne particles are of increasing concern in society. In order to protect public health, a clarification of the toxic properties of particles from different sources is of importance. The aim of this study was to investigate and compare the genotoxicity and the ability to induce inflammatory mediators of nine different particle types from wood and pellets combustion, from tire–road wear and collected from an urban street and a subway station. The comet assay was used to assess genotoxicity after exposure of the human lung cell line A549. Inflammatory effects were measured as induction of IL-6, IL-8 and TNF-α after exposure of human macrophages. We found that all particles tested caused DNA damage and those from the subway caused more damage than the other particles (p < 0.001) likely due to redox-active iron. In contrast, particles collected from an urban street were most potent to induce inflammatory cytokines. Particles from tire–road wear collected using a road simulator were genotoxic and able to induce cytokines. Finally, more effective combustion of wood led to less emission of particles, but those emitted did not show less toxicity in this study.

  • 4.
    Karlsson, Helen
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Arbets- och miljömedicin.
    Lindbom, John
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Ghafouri, Bijar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Smärt och rehabiliteringscentrum. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Arbets- och miljömedicin.
    Lindahl, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Tagesson, Christer
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Arbets- och miljömedicin.
    Gustafsson, Mats
    Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Arbets- och miljömedicin.
    Ljungman, Anders G
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Wear Particles from Studded Tires and Granite Pavement Induce Pro-inflammatory Alterations in Human Monocyte-Derived Macrophages: A Proteomic Study.2011Inngår i: Chemical Research in Toxicology, ISSN 0893-228X, E-ISSN 1520-5010, Vol. 24, s. 45-53Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Airborne particulate matter is considered to be one of the environmental contributors to the mortality in cancer, respiratory, and cardiovascular diseases. For future preventive actions, it is of major concern to investigate the toxicity of defined groups of airborne particles and to clarify their pathways in biological tissues. To expand the knowledge beyond general inflammatory markers, this study examined the toxicoproteomic effects on human monocyte derived macrophages after exposure to wear particles generated from the interface of studded tires and a granite-containing pavement. As comparison, the effect of endotoxin was also investigated. The macrophage proteome was separated using two-dimensional gel electrophoresis. Detected proteins were quantified, and selected proteins were identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry. Among analyzed proteins, seven were significantly decreased and three were increased by exposure to wear particles as compared to unexposed control cells. Endotoxin exposure resulted in significant changes in the expression of six proteins: four decreased and two increased. For example, macrophage capping protein was significantly increased after wear particle exposure only, whereas calgizzarin and galectin-3 were increased by both wear particle and endotoxin exposure. Overall, proteins associated with inflammatory response were increased and proteins involved in cellular functions such as redox balance, anti-inflammatory response, and glycolysis were decreased. Investigating the effects of characterized wear particles on human macrophages with a toxicoproteomic approach has shown to be useful in the search for more detailed information about specific pathways and possible biological markers.

  • 5.
    Lindbom, John
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Phospholipase A2 expression in the human nasal mucosa2004Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Phospholipase A2 (PLA2) is a superfamily of enzymes that promote inflammation by releasing arachidonic acid for the synthesis of eicosanoids and lysophospholipid for the synthesis of platelet-activating factor (PAF). On the other hand, several members of the PLA2 family (VIIA, VIIB, VIIIA and VIIIB) are able to degrade PAF and are therefore potentially important anti-inflammatory enzymes. The precise roles of the different PLA2 enzymes in airways inflammation are not known and the gene expression of the different PLA2s in the human nasal mucosa has not previously been examined. Using reversed transcription-polymerase chain reaction (RT-PCR) techniques, this thesis investigated (i) the occurrence of mRNAs for different PLA2 types in the nasal mucosa of healthy subjects; (ii) the effects of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) on the gene expression of different PLA2s in human nasal epithelial cells (RPMI 2650); (iii) the effects of IFN-γ and lipopolysaccharide (LPS) on the gene expression of different PLA2 types in human monocyte-derived macrophages; (iv) the effects of exudates from LPS- or ß-glucan exposed macrophages on the gene expression of different PLA2 types in RPMI 2650 cells, and (v) the levels of different PLA2 mRNAs in the nasal mucosa of patients with seasonal allergic rhinitis (SAR) and healthy controls. The relative abundances of the different PLA2 transcripts in normal human nasal mucosa were found to be X ≈ IVA > IIA ≈ IIE ≈ IVB ≈ VI > IB ≈ IID ≈ III ≈ IVC ≈ VII ≈ VIB. In RPMI 2650 cells, TNF-α increased the expression of PLA2 IVA and IVC, while IFN-γ increased the expression of PLA2 IIA and IID. In macrophages, IFN-γ increased the expression of both PLA2 IID and IVA while LPS increased the expression of PLA2 IVA but decreased that of IID. Medium from macrophages exposed to LPS or ß-glucan increased the expression of PLA2 IVC in RPMI 2650 cells; this upregulation was abrogated by antibodies to TNF-α and by the nuclear factor (NF)-κB inhibitor, pyrrolidine dithiocarbamate. Notably, the mRNA levels of PLA2 VIIA (PAF acetylhydrolase I) were lower in SAR patients than controls during both the pollen season and the off-season for pollen. These findings demonstrate that a large number of PLA2 types are constitutively expressed in the normal human nasal mucosa, including the newly discovered PLA2 types IID, IIE, IIF, III, IVB, IVC, VIB, X, XIIA, and XIIB. They also demonstrate that TNF-α and IFN-γ cause increased gene expression of two novel cytosolic and secretory PLA2 types (IVC and IID, respectively) in human nasal epithelial cells, suggesting that these PLA2 types may be involved in cytokine-mediated inflammation in the nasal mucosa. Moreover, the findings indicate that both LPS- and ß-glucan-activated macrophages can induce the gene expression of PLA2 IVC in nasal epithelial cells, and that this upregulation is mediated through TNF-α and under NF-κB control. The observation that PAF acetylhydrolase mRNA expression in the nasal mucosa is lower in SAR patients than in healthy subjects points to the possibility that impaired ability to inactivate PAF might be of importance in SAR.

    Delarbeid
    1. Expression of members of the phospholipase A2 family of enzymes in human nasal mucosa
    Åpne denne publikasjonen i ny fane eller vindu >>Expression of members of the phospholipase A2 family of enzymes in human nasal mucosa
    2001 (engelsk)Inngår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 18, nr 1, s. 130-138Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Phospholipase A2 (PLA2) is a family of enzymes thought to play a key role in inflammation by releasing arachidonic acid for the synthesis of eicosanoids and lysophospholipid for the synthesis of platelet-activating factor. However, the precise contribution of different PLA2 types to the formation of inflammatory lipid mediators in the upper airways is not known and the expression of different PLA2 genes in the human nasal mucosa has not been examined.

    This study therefore investigated the occurrence of messenger ribonucleic acids (mRNAs) for different PLA2 forms (IB, IIA, IID, IIE, III, IVA, IVB, IVC, V, VI, VII, X, acid calcium-independent (aiPLA2), and calcium-independent membrane bound PLA2, (iPLA2-2)) in the nasal mucosa of five healthy human subjects.

    Using reversed transcription-polymerase chain reaction (RT-PCR) techniques it was found that all these PLA2 types except PLA2 V were expressed in all subjects, whereas PLA2 V was detected in only one individual on one single occasion. The relative abundance of the different PLA2 transcripts were aiPLA2>X≈IVA>IIA≈IIE≈IVB≈VI>IB≈IID≈III≈IVC≈VII≈iPLA2-2. To further quantify the mRNA-expression of PLA2 X, IVA and IIA, the samples were reanalysed with a quantitative PCR-technique utilizing competitive deoxyribonucleic acid (DNA) mimics as references. The amounts of PLA2 X, IVA and IIA mRNA were then estimated to 0.9±0.2, 1.1±0.7, and 0.0025±0.0021 amol (mean±se), respectively, confirming the relative abundance of these PLA2 transcripts and indicating that the recently described PLA2 X form is relatively strongly expressed.

    These findings demonstrate that a large number of PLA2 types are expressed in the normal human nasal mucosa. Moreover, this investigation demonstrates, for the first time, the presence of the newly discovered phospholipase A2 forms IID, IIE, III, IVB, IVC, X and calcium-independent membrane bound phospholipase A2 in the human nasal mucosa and raises the possibility that one or several of these may be involved in inflammatory reactions in the nose.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-26015 (URN)10.1183/09031936.01.00054701 (DOI)10468 (Lokal ID)10468 (Arkivnummer)10468 (OAI)
    Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2017-12-13
    2. Increased gene expression of novel cytosolic and secretory phospholipase A2 types in human airway epithelial cells induced by tumor necrosis factor-α and IFN-γ
    Åpne denne publikasjonen i ny fane eller vindu >>Increased gene expression of novel cytosolic and secretory phospholipase A2 types in human airway epithelial cells induced by tumor necrosis factor-α and IFN-γ
    2002 (engelsk)Inngår i: Journal of Interferon and Cytokine Research, ISSN 1079-9907, E-ISSN 1557-7465, Vol. 22, nr 9, s. 947-955Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Phospholipase A2 (PLA2) is a growing family of enzymes that may play a major role in inflammation. We investigated the effect of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) on the gene expression of 19 different PLA2 types (IB, IIA, IID, IIE, IIF, III, IVA, IVB, IVC, V, VIA, VIB, VIIA, VIIB, VIIIA, VIIIB, X, XII, and XIII) in human bronchoepithelial (BEAS-2B) and nasal epithelial (RPMI 2650) cells. The cells were stimulated with TNF-α or IFN-γ for different lengths of time (1, 4, 18, and 48 h), and the mRNA levels of the different PLA2 types were determined by reverse transcriptase-PCR (RT-PCR) and normalized to those of the housekeeping gene, GAPDH. In both cell lines, TNF-α increased the expression of PLA2 IVA and IVC, and IFN-γ increased the expression of PLA2 IIA and IID. No influence on the gene expression of PLA2-activating protein (PLAP) was noted on cytokine stimulation. These findings indicate that TNF-α and IFN-γ induce gene expression of two novel cytosolic and secretory PLA2 types (IVC and IID, respectively) in human airway epithelial cells. The possibility that these PLA2 types are involved in cytokine-mediated inflammation in the respiratory tract is inferred.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-26517 (URN)10.1089/10799900260286650 (DOI)11075 (Lokal ID)11075 (Arkivnummer)11075 (OAI)
    Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2017-12-13
    3. Interferon γ-induced gene expression of the novel secretory phospholipase A2 type IID in human monocyte-derived macrophages is inhibited by lipopolysaccharide
    Åpne denne publikasjonen i ny fane eller vindu >>Interferon γ-induced gene expression of the novel secretory phospholipase A2 type IID in human monocyte-derived macrophages is inhibited by lipopolysaccharide
    2005 (engelsk)Inngår i: Inflammation, ISSN 0360-3997, E-ISSN 1573-2576, Vol. 29, nr 2-3, s. 108-117Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Phospholipase A2 (PLA2) is a superfamily of enzymes that may play a major role in airways inflammation. We investigated the effect of interferon-γ (IFN-γ) on the gene expression of 19 different PLA2 types in human monocyte-derived macrophages and nasal epithelial cells (RPMI 2650). The cells were stimulated with IFN-γ for different lengths of time (up to 48 h), and the mRNA levels of the different PLA2 types were determined by reverse transcriptase–PCR (RT-PCR) and normalized to those of the house-keeping gene, GAPDH. It appeared that IFN-γ clearly increased the expression of secretory PLA2 IID (but not IIA) in macrophages, while both PLA2 IID and IIA were upregulated in RPMI 2650 cells. Moreover, after 18 h, the mRNA levels of cytosolic PLA2 IVA were 2–3 times higher in IFN-γ-stimulated macrophages than controls, while there was no such effect of IFN-γ in RPMI 2650 cells. Lipopolysaccharide (LPS) augmented the increased gene expression of PLA2 IVA but decreased both the basal and the IFN-γ-induced PLA2 IID mRNA expression in macrophages (but not in RPMI 2650 cells). The NF-κB inhibitor Pyrrolidine dithiocarbamate (PDTC) and the phoshatidylinositol 3-kinase (PI3K) inhibitor wortmannin were employed to get an insight into the mechanism behind these observations. Incubation of macrophages with PDTC had no effect on the LPS impairment of PLA2 IID gene expression, but inhibited the LPS mediated activation of PLA2 IVA. No significant effect was noted of PDTC on IFN-γ stimulation, while PI3K had no effect at all on any of the stimuli used. Furthermore, LPS (but not IFN-γ) increased the mRNA levels of the nuclear factor (NF)-κB inhibitors α and ξ in macrophages, but not in RPMI 2650 cells. These findings indicate that (a) the gene expression of secretory types PLA2 IID and IIA in response to IFN-γ is much dependent on cell type, and (b) the regulation of PLA2 type IID in human macrophages is clearly different from that of PLA2 type IVA. (c) PLA2 IVA is probably under control of both NF-κB and IFN-γ-responsive elements (GRE) or IFN-γ-activating sites (GAS). The possibility that PLA2 IID is involved in cytokine-mediated inflammation in the nasal mucosa is inferred, as is the potential role of PLA2 IID in the host defense against LPS-containing bacteria.

    Emneord
    IFN-?, LPS, Macrophages, Nasal mucosa, PLA2
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-45483 (URN)10.1007/s10753-006-9007-x (DOI)
    Tilgjengelig fra: 2009-10-11 Laget: 2009-10-11 Sist oppdatert: 2017-12-13
    4. Lipopolysaccharide- and ß-glucan-stimulated macrophages upregulate cytolosic phospholipase A2 IVC in nasal epithelial cells: role of TNF-α
    Åpne denne publikasjonen i ny fane eller vindu >>Lipopolysaccharide- and ß-glucan-stimulated macrophages upregulate cytolosic phospholipase A2 IVC in nasal epithelial cells: role of TNF-α
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Phospholipase A2 (PLA2) is a superfamily of enzymes that may play a major role in airways inflammation. We investigated the gene expression of 20 different PLA2 types in nasal epithelial cells (RPMI 2650) before and after incubation with cell growth medium from human monocyte-derived macrophages exposed to lipopolysaccharide (LPS) or ß-1,3-D-glucan (ßG). The macropbages were exposed to LPS (10 µ/ml) or ßG (500 µg/ml) for 48 hours and the mRNA levels of the different PLA2 types in RPMI 2650 cells were determined after incubation for 18 hours using reverse transcriptase-PCR (RT-PCR). It appeared that the mRNA levels of PLA2 type IVC were significantly increased after incubation, both with medium from LPS-exposed and ßG-exposed macrophages. In both cases, the increased PLA2 IVA mRNA expression was abolished by TNF-α antibodies and by the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC). There were no significant alterations in the mRNA levels of the other PLA2 types, including PLA2 IVA. These findings indicate that both LPS- and ßG-activated macrophages can induce the gene expression of PLA2 IVC in nasal epithelial cells, and that this upregulation is mediated through TNF-α and under NF-κB control. Further studies are required to clarify whether these mechanisms may operate to cause inflammation in the nasal mucosa in vivo.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-84953 (URN)
    Tilgjengelig fra: 2012-10-29 Laget: 2012-10-29 Sist oppdatert: 2012-10-29
    5. Phospholipase A2 mRNA expression in the nasal mucosa of healthy subjects and patients with seasonal allergic rhinitis
    Åpne denne publikasjonen i ny fane eller vindu >>Phospholipase A2 mRNA expression in the nasal mucosa of healthy subjects and patients with seasonal allergic rhinitis
    Vise andre…
    2004 (engelsk)Inngår i: Rhinology, ISSN 0300-0729, E-ISSN 1996-8604, Vol. 42, nr 2, s. 85-91Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Phospholipase A2 (PLA2) is a family of enzymes that play different role(s) in inflammation, but their importance in seasonal allergic rhinitis (SAR) has not been clarified. Here, we determined the levels of messenger ribonucleic acid (mRNA) for different PLA2 types in the nasal mucosa of SAR patients (n=6) and healthy controls (n=5). Nasal brush samples were taken both during pollen season, when the symptoms of the patients were severe, and off-season, when the patients were free of symptoms. We found that PLA2 IB, IIA, IID,IIE, IIF III, IVA, IVB, IVC, VIA, VIB, VIIA, VIIB, VIIIA, VIIIB, X, XII and XIII were all expressed in each subject at both occasions. The mRNA levels of PLA2 VIIA (platelet-activating factor (PAF) acetylhydrolase) were lower in SAR patients than controls, both during pollen season (p = 0.03) and off season (p = 0.03). These findings demonstrate that a large number of PLA2 types are expressed in the nasal mucosa, regardless of whether there is ongoing allergic inflammation or not. The observation that PAF acetylhydrolase mRNA expression in the nasal mucosa is lower in SAR patients than in healthy subjects suggests the possibility that impaired ability to inactivate PAF might be of importance in SAR. Further studies are required to clarify whether the decreased PAF acetylhydrolase mRNA expression in SAR is accompanied by decreased enzyme activity and whether aberrations in PAF acetylhydrolase are present in infectious rhinitis patients as well.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-22328 (URN)15224635 (PubMedID)1528 (Lokal ID)1528 (Arkivnummer)1528 (OAI)
    Tilgjengelig fra: 2009-10-07 Laget: 2009-10-07 Sist oppdatert: 2017-12-13bibliografisk kontrollert
  • 6.
    Lindbom, John
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Phospholipase A2 expression in the human nasal mucosa2002Licentiatavhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Phospholipase A2 (PLA2) is a superfamily of enzymes that play a key role in inflammation by releasing arachidonic acid for the synthesis of eicosanoids and lysophospholipid for the synthesis of platelet-activating factor (PAF). On the other hand, several members of the PLA2 family (VIIA, VIIB, VIIIA and VIIIB) are able to degrade PAF and are therefore potentially important anti-inflammatory enzymes. The precise roles of the different PLA2 enzymes in airway inflammation are not known and the gene expression of the different PLA2s in the human nasal mucosa has not previously been examined. Using reversed transcriptionpolymerase chain reaction (RT-PCR) techniques, this thesis investigated (i) the occurrence of mRNAs for different PLA2 types in the nasal mucosa of healthy subjects; (ii) the levels of different PLA2 mRNAs in the nasal mucosa of patients with seasonal allergic rhinitis (SAR) and healthy controls, and (iii) the effect of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) on the gene expression of different PLA2s in human nasal (RPMI 2650) and bronchoepithelial (BEAS-2B) cells.

    The relative abundances of the different PLA2 transcripts in normal human nasal mucosa were found to be X ≈ IVA > IIA ≈ IIE ≈ IVB ≈ VI > IB ≈ IID ≈ III ≈ IVC ≈ VII ≈ VIB. Notably, the mRNA levels of PLA2 VIIA (PAF acetylhydrolase I) were lower in SAR patients than controls during both the pollen season and the off-season for pollen. In both cell lines, TNF-α increased the expression of PLA2 IVA and IVC, while IFN-γ increased the expression of PLA2 IIA and IID. These findings demonstrate that a large number of PLA2 types are constitutively expressed in the normal human nasal mucosa, and they also demonstrate the presence of the newly discovered PLA2 types IID, IIE, IIF, III, IVB, IVC, VIB, X, XII, and XIII. Moreover, the findings indicate that TNF-α and IFN-γ cause increased gene expression of two novel cytosolic and secretory PLA2 types (IVC and IID, respectively) in human airway epithelial cells, suggesting that these PLA2 types may be involved in cytokine-mediated inflammation in the respiratory tract. The observation that PAF acetylhydrolase mRNA expression in the nasal mucosa is lower in SAR patients than in healthy subjects suggests the possibility that impaired ability to inactivate PAF might be of in1portance in SAR.

    Delarbeid
    1. Expression of members of the phospholipase A2 family of enzymes in human nasal mucosa
    Åpne denne publikasjonen i ny fane eller vindu >>Expression of members of the phospholipase A2 family of enzymes in human nasal mucosa
    2001 (engelsk)Inngår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 18, nr 1, s. 130-138Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Phospholipase A2 (PLA2) is a family of enzymes thought to play a key role in inflammation by releasing arachidonic acid for the synthesis of eicosanoids and lysophospholipid for the synthesis of platelet-activating factor. However, the precise contribution of different PLA2 types to the formation of inflammatory lipid mediators in the upper airways is not known and the expression of different PLA2 genes in the human nasal mucosa has not been examined.

    This study therefore investigated the occurrence of messenger ribonucleic acids (mRNAs) for different PLA2 forms (IB, IIA, IID, IIE, III, IVA, IVB, IVC, V, VI, VII, X, acid calcium-independent (aiPLA2), and calcium-independent membrane bound PLA2, (iPLA2-2)) in the nasal mucosa of five healthy human subjects.

    Using reversed transcription-polymerase chain reaction (RT-PCR) techniques it was found that all these PLA2 types except PLA2 V were expressed in all subjects, whereas PLA2 V was detected in only one individual on one single occasion. The relative abundance of the different PLA2 transcripts were aiPLA2>X≈IVA>IIA≈IIE≈IVB≈VI>IB≈IID≈III≈IVC≈VII≈iPLA2-2. To further quantify the mRNA-expression of PLA2 X, IVA and IIA, the samples were reanalysed with a quantitative PCR-technique utilizing competitive deoxyribonucleic acid (DNA) mimics as references. The amounts of PLA2 X, IVA and IIA mRNA were then estimated to 0.9±0.2, 1.1±0.7, and 0.0025±0.0021 amol (mean±se), respectively, confirming the relative abundance of these PLA2 transcripts and indicating that the recently described PLA2 X form is relatively strongly expressed.

    These findings demonstrate that a large number of PLA2 types are expressed in the normal human nasal mucosa. Moreover, this investigation demonstrates, for the first time, the presence of the newly discovered phospholipase A2 forms IID, IIE, III, IVB, IVC, X and calcium-independent membrane bound phospholipase A2 in the human nasal mucosa and raises the possibility that one or several of these may be involved in inflammatory reactions in the nose.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-26015 (URN)10.1183/09031936.01.00054701 (DOI)10468 (Lokal ID)10468 (Arkivnummer)10468 (OAI)
    Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2017-12-13
    2. Phospholipase A2 mRNA expression in the nasal mucosa of healthy subjects and patients with seasonal allergic rhinitis
    Åpne denne publikasjonen i ny fane eller vindu >>Phospholipase A2 mRNA expression in the nasal mucosa of healthy subjects and patients with seasonal allergic rhinitis
    Vise andre…
    2004 (engelsk)Inngår i: Rhinology, ISSN 0300-0729, E-ISSN 1996-8604, Vol. 42, nr 2, s. 85-91Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Phospholipase A2 (PLA2) is a family of enzymes that play different role(s) in inflammation, but their importance in seasonal allergic rhinitis (SAR) has not been clarified. Here, we determined the levels of messenger ribonucleic acid (mRNA) for different PLA2 types in the nasal mucosa of SAR patients (n=6) and healthy controls (n=5). Nasal brush samples were taken both during pollen season, when the symptoms of the patients were severe, and off-season, when the patients were free of symptoms. We found that PLA2 IB, IIA, IID,IIE, IIF III, IVA, IVB, IVC, VIA, VIB, VIIA, VIIB, VIIIA, VIIIB, X, XII and XIII were all expressed in each subject at both occasions. The mRNA levels of PLA2 VIIA (platelet-activating factor (PAF) acetylhydrolase) were lower in SAR patients than controls, both during pollen season (p = 0.03) and off season (p = 0.03). These findings demonstrate that a large number of PLA2 types are expressed in the nasal mucosa, regardless of whether there is ongoing allergic inflammation or not. The observation that PAF acetylhydrolase mRNA expression in the nasal mucosa is lower in SAR patients than in healthy subjects suggests the possibility that impaired ability to inactivate PAF might be of importance in SAR. Further studies are required to clarify whether the decreased PAF acetylhydrolase mRNA expression in SAR is accompanied by decreased enzyme activity and whether aberrations in PAF acetylhydrolase are present in infectious rhinitis patients as well.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-22328 (URN)15224635 (PubMedID)1528 (Lokal ID)1528 (Arkivnummer)1528 (OAI)
    Tilgjengelig fra: 2009-10-07 Laget: 2009-10-07 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    3. Increased gene expression of novel cytosolic and secretory phospholipase A2 types in human airway epithelial cells induced by tumor necrosis factor-α and IFN-γ
    Åpne denne publikasjonen i ny fane eller vindu >>Increased gene expression of novel cytosolic and secretory phospholipase A2 types in human airway epithelial cells induced by tumor necrosis factor-α and IFN-γ
    2002 (engelsk)Inngår i: Journal of Interferon and Cytokine Research, ISSN 1079-9907, E-ISSN 1557-7465, Vol. 22, nr 9, s. 947-955Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Phospholipase A2 (PLA2) is a growing family of enzymes that may play a major role in inflammation. We investigated the effect of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) on the gene expression of 19 different PLA2 types (IB, IIA, IID, IIE, IIF, III, IVA, IVB, IVC, V, VIA, VIB, VIIA, VIIB, VIIIA, VIIIB, X, XII, and XIII) in human bronchoepithelial (BEAS-2B) and nasal epithelial (RPMI 2650) cells. The cells were stimulated with TNF-α or IFN-γ for different lengths of time (1, 4, 18, and 48 h), and the mRNA levels of the different PLA2 types were determined by reverse transcriptase-PCR (RT-PCR) and normalized to those of the housekeeping gene, GAPDH. In both cell lines, TNF-α increased the expression of PLA2 IVA and IVC, and IFN-γ increased the expression of PLA2 IIA and IID. No influence on the gene expression of PLA2-activating protein (PLAP) was noted on cytokine stimulation. These findings indicate that TNF-α and IFN-γ induce gene expression of two novel cytosolic and secretory PLA2 types (IVC and IID, respectively) in human airway epithelial cells. The possibility that these PLA2 types are involved in cytokine-mediated inflammation in the respiratory tract is inferred.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-26517 (URN)10.1089/10799900260286650 (DOI)11075 (Lokal ID)11075 (Arkivnummer)11075 (OAI)
    Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2017-12-13
  • 7.
    Lindbom, John
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Gustafsson, Mats
    Swedish National Road and Transport Research Institute, Linköping, Sweden.
    Blomqvist, Göran
    Swedish National Road and Transport Research Institute, Linköping, Sweden.
    Dahl, Andreas
    Division of Ergonomics and Aerosol Technology, Lund University, Lund, Sweden.
    Gudmundsson, Anders
    Division of Ergonomics and Aerosol Technology, Lund University, Lund, Sweden.
    Swietlicki, Erik
    Division of Nuclear Physics, Lund University, Lund, Sweden.
    Ljungman, Anders
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Exposure to wear particles generated from studded tires and pavement induces inflammatory cytokine release from human macrophages2006Inngår i: Chemical Research in Toxicology, ISSN 0893-228X, E-ISSN 1520-5010, Vol. 19, nr 4, s. 521-530Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Health risks associated with exposure to airborne paniculate matter (PM) have been shown epidemiologically as well as experimentally, pointing to both respiratory and cardiovascular effects. Lately, wear particles generated from traffic have been recognized to be a major contributing source to the overall particle load, especially in the Nordic countries were studded tires are used. In this work, we investigated the inflammatory effect of PM10 generated from the wear of studded tires on two different types of pavement. As comparison, we also investigated PM10 from a traffic-intensive street, a subway station, and diesel exhaust particles (DEP). Human monocyte-derived macrophages, nasal epithelial cells (RPMI 2650), and bronchial epithelial cells (BEAS-2B) were exposed to the different types of particles, and the secretion of IL-6, IL-8, IL-10, and TNF-α into the culture medium was measured. The results show a significant release of cytokines from macrophages after exposure for all types of particles. When particles generated from asphalt/granite pavement were compared to asphalt/quartzite pavement, the granite pavement had a significantly higher capacity to induce the release of cytokines. The granite pavement particles induced cytokine release at the same magnitude as the street particles did, which was higher than what particles from both a subway station and DEP did. Exposure of epithelial cells to PM 10 resulted in a significant increase of TNF-α secreted from BEAS-2B cells for all types of particles used (DEP was not tested), and the highest levels were induced by subway particles. None of the particle types were able to evoke detectable cytokine release from RPMI 2650 cells. The results indicate that PM10 generated by the wear of studded tires on the street surface is a large contributor to the cytokine-releasing ability of particles in traffic-intensive areas and that the type of pavement used is important for the level of this contribution. Furthermore, the airway inflammatory potential of wear particles from tires and pavement might be of a greater magnitude than that of DEP.

  • 8.
    Lindbom, John
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Gustafsson, Mats
    Swedish National Road and Transport Research Institute, Linköping, Sweden.
    Blomqvist, Göran
    Swedish National Road and Transport Research Institute, Linköping, Sweden.
    Dahl, Andreas
    Division of Ergonomics and Aerosol Technology, Lund University, Lund, Sweden.
    Gudmundsson, Anders
    Division of Ergonomics and Aerosol Technology, Lund University, Lund, Sweden.
    Swietlicki, Erik
    Division of Nuclear Physics, Lund University, Lund, Sweden.
    Ljungman, Anders
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Wear particles generated from studded tires and pavement induces inflammatory reactions in mouse macrophage cells2007Inngår i: Chemical Research in Toxicology, ISSN 0893-228X, E-ISSN 1520-5010, Vol. 20, nr 6, s. 937-946Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Health risks associated with exposure to airborne particulate matter (PM) have been shown epidemiologically as well as experimentally, pointing to both respiratory and cardiovascular effects. These health risks are of increasing concern in society, and to protect public health, a clarification of the toxic properties of particles from different sources is of importance. Lately, wear particles generated from traffic have been recognized as a major contributing source to the overall particle load, especially in the Nordic countries where studded tires are used. The aim of this study was to further investigate and compare the ability to induce inflammatory mediators of different traffic-related wear particles collected from an urban street, a subway station, and studded tire-pavement wear. Inflammatory effects were measured as induction of nitric oxide (NO), IL-6, TNF-α, arachidonic acid (AA), and lipid peroxidation after exposure of the murine macrophage like cell line RAW 264.7. In addition, the redox potential of the particles was measured in a cell-free system. The results show that all particles tested induce IL-6, TNF-α, and NO, and those from the urban street were the most potent ones. In contrast, particles collected from a subway station were most potent to induce lipid peroxidation, A A release, and formation of ROS. Particles from studded tire-pavement wear, generated using a road simulator, were able to induce inflammatory cytokines, NO, lipid peroxidation, and ROS formation. Interestingly, particles generated from pavement containing granite as the main stone material were more potent than those generated from pavement containing quartzite as the main stone material.

  • 9.
    Lindbom, John
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Ljungman, Anders G.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Tagesson, Christer
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Lipopolysaccharide- and ß-glucan-stimulated macrophages upregulate cytolosic phospholipase A2 IVC in nasal epithelial cells: role of TNF-αManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Phospholipase A2 (PLA2) is a superfamily of enzymes that may play a major role in airways inflammation. We investigated the gene expression of 20 different PLA2 types in nasal epithelial cells (RPMI 2650) before and after incubation with cell growth medium from human monocyte-derived macrophages exposed to lipopolysaccharide (LPS) or ß-1,3-D-glucan (ßG). The macropbages were exposed to LPS (10 µ/ml) or ßG (500 µg/ml) for 48 hours and the mRNA levels of the different PLA2 types in RPMI 2650 cells were determined after incubation for 18 hours using reverse transcriptase-PCR (RT-PCR). It appeared that the mRNA levels of PLA2 type IVC were significantly increased after incubation, both with medium from LPS-exposed and ßG-exposed macrophages. In both cases, the increased PLA2 IVA mRNA expression was abolished by TNF-α antibodies and by the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC). There were no significant alterations in the mRNA levels of the other PLA2 types, including PLA2 IVA. These findings indicate that both LPS- and ßG-activated macrophages can induce the gene expression of PLA2 IVC in nasal epithelial cells, and that this upregulation is mediated through TNF-α and under NF-κB control. Further studies are required to clarify whether these mechanisms may operate to cause inflammation in the nasal mucosa in vivo.

  • 10.
    Lindbom, John
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Ljungman, Anders
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Irander, Kristina
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Lindahl, Mats
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Tagesson, Christer
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Phospholipase A2 mRNA expression in the nasal mucosa of healthy subjects and patients with seasonal allergic rhinitis2004Inngår i: Rhinology, ISSN 0300-0729, E-ISSN 1996-8604, Vol. 42, nr 2, s. 85-91Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Phospholipase A2 (PLA2) is a family of enzymes that play different role(s) in inflammation, but their importance in seasonal allergic rhinitis (SAR) has not been clarified. Here, we determined the levels of messenger ribonucleic acid (mRNA) for different PLA2 types in the nasal mucosa of SAR patients (n=6) and healthy controls (n=5). Nasal brush samples were taken both during pollen season, when the symptoms of the patients were severe, and off-season, when the patients were free of symptoms. We found that PLA2 IB, IIA, IID,IIE, IIF III, IVA, IVB, IVC, VIA, VIB, VIIA, VIIB, VIIIA, VIIIB, X, XII and XIII were all expressed in each subject at both occasions. The mRNA levels of PLA2 VIIA (platelet-activating factor (PAF) acetylhydrolase) were lower in SAR patients than controls, both during pollen season (p = 0.03) and off season (p = 0.03). These findings demonstrate that a large number of PLA2 types are expressed in the nasal mucosa, regardless of whether there is ongoing allergic inflammation or not. The observation that PAF acetylhydrolase mRNA expression in the nasal mucosa is lower in SAR patients than in healthy subjects suggests the possibility that impaired ability to inactivate PAF might be of importance in SAR. Further studies are required to clarify whether the decreased PAF acetylhydrolase mRNA expression in SAR is accompanied by decreased enzyme activity and whether aberrations in PAF acetylhydrolase are present in infectious rhinitis patients as well.

  • 11.
    Lindbom, John
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Ljungman, Anders
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Lindahl, Mats
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Tagesson, Christer
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Expression of members of the phospholipase A2 family of enzymes in human nasal mucosa2001Inngår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 18, nr 1, s. 130-138Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Phospholipase A2 (PLA2) is a family of enzymes thought to play a key role in inflammation by releasing arachidonic acid for the synthesis of eicosanoids and lysophospholipid for the synthesis of platelet-activating factor. However, the precise contribution of different PLA2 types to the formation of inflammatory lipid mediators in the upper airways is not known and the expression of different PLA2 genes in the human nasal mucosa has not been examined.

    This study therefore investigated the occurrence of messenger ribonucleic acids (mRNAs) for different PLA2 forms (IB, IIA, IID, IIE, III, IVA, IVB, IVC, V, VI, VII, X, acid calcium-independent (aiPLA2), and calcium-independent membrane bound PLA2, (iPLA2-2)) in the nasal mucosa of five healthy human subjects.

    Using reversed transcription-polymerase chain reaction (RT-PCR) techniques it was found that all these PLA2 types except PLA2 V were expressed in all subjects, whereas PLA2 V was detected in only one individual on one single occasion. The relative abundance of the different PLA2 transcripts were aiPLA2>X≈IVA>IIA≈IIE≈IVB≈VI>IB≈IID≈III≈IVC≈VII≈iPLA2-2. To further quantify the mRNA-expression of PLA2 X, IVA and IIA, the samples were reanalysed with a quantitative PCR-technique utilizing competitive deoxyribonucleic acid (DNA) mimics as references. The amounts of PLA2 X, IVA and IIA mRNA were then estimated to 0.9±0.2, 1.1±0.7, and 0.0025±0.0021 amol (mean±se), respectively, confirming the relative abundance of these PLA2 transcripts and indicating that the recently described PLA2 X form is relatively strongly expressed.

    These findings demonstrate that a large number of PLA2 types are expressed in the normal human nasal mucosa. Moreover, this investigation demonstrates, for the first time, the presence of the newly discovered phospholipase A2 forms IID, IIE, III, IVB, IVC, X and calcium-independent membrane bound phospholipase A2 in the human nasal mucosa and raises the possibility that one or several of these may be involved in inflammatory reactions in the nose.

  • 12.
    Lindbom, John
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Ljungman, Anders
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Lindahl, Mats
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Tagesson, Christer
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Increased gene expression of novel cytosolic and secretory phospholipase A2 types in human airway epithelial cells induced by tumor necrosis factor-α and IFN-γ2002Inngår i: Journal of Interferon and Cytokine Research, ISSN 1079-9907, E-ISSN 1557-7465, Vol. 22, nr 9, s. 947-955Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Phospholipase A2 (PLA2) is a growing family of enzymes that may play a major role in inflammation. We investigated the effect of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) on the gene expression of 19 different PLA2 types (IB, IIA, IID, IIE, IIF, III, IVA, IVB, IVC, V, VIA, VIB, VIIA, VIIB, VIIIA, VIIIB, X, XII, and XIII) in human bronchoepithelial (BEAS-2B) and nasal epithelial (RPMI 2650) cells. The cells were stimulated with TNF-α or IFN-γ for different lengths of time (1, 4, 18, and 48 h), and the mRNA levels of the different PLA2 types were determined by reverse transcriptase-PCR (RT-PCR) and normalized to those of the housekeeping gene, GAPDH. In both cell lines, TNF-α increased the expression of PLA2 IVA and IVC, and IFN-γ increased the expression of PLA2 IIA and IID. No influence on the gene expression of PLA2-activating protein (PLAP) was noted on cytokine stimulation. These findings indicate that TNF-α and IFN-γ induce gene expression of two novel cytosolic and secretory PLA2 types (IVC and IID, respectively) in human airway epithelial cells. The possibility that these PLA2 types are involved in cytokine-mediated inflammation in the respiratory tract is inferred.

  • 13.
    Lindbom, John
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Ljungman, Anders
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Tagesson, Christer
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Interferon γ-induced gene expression of the novel secretory phospholipase A2 type IID in human monocyte-derived macrophages is inhibited by lipopolysaccharide2005Inngår i: Inflammation, ISSN 0360-3997, E-ISSN 1573-2576, Vol. 29, nr 2-3, s. 108-117Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Phospholipase A2 (PLA2) is a superfamily of enzymes that may play a major role in airways inflammation. We investigated the effect of interferon-γ (IFN-γ) on the gene expression of 19 different PLA2 types in human monocyte-derived macrophages and nasal epithelial cells (RPMI 2650). The cells were stimulated with IFN-γ for different lengths of time (up to 48 h), and the mRNA levels of the different PLA2 types were determined by reverse transcriptase–PCR (RT-PCR) and normalized to those of the house-keeping gene, GAPDH. It appeared that IFN-γ clearly increased the expression of secretory PLA2 IID (but not IIA) in macrophages, while both PLA2 IID and IIA were upregulated in RPMI 2650 cells. Moreover, after 18 h, the mRNA levels of cytosolic PLA2 IVA were 2–3 times higher in IFN-γ-stimulated macrophages than controls, while there was no such effect of IFN-γ in RPMI 2650 cells. Lipopolysaccharide (LPS) augmented the increased gene expression of PLA2 IVA but decreased both the basal and the IFN-γ-induced PLA2 IID mRNA expression in macrophages (but not in RPMI 2650 cells). The NF-κB inhibitor Pyrrolidine dithiocarbamate (PDTC) and the phoshatidylinositol 3-kinase (PI3K) inhibitor wortmannin were employed to get an insight into the mechanism behind these observations. Incubation of macrophages with PDTC had no effect on the LPS impairment of PLA2 IID gene expression, but inhibited the LPS mediated activation of PLA2 IVA. No significant effect was noted of PDTC on IFN-γ stimulation, while PI3K had no effect at all on any of the stimuli used. Furthermore, LPS (but not IFN-γ) increased the mRNA levels of the nuclear factor (NF)-κB inhibitors α and ξ in macrophages, but not in RPMI 2650 cells. These findings indicate that (a) the gene expression of secretory types PLA2 IID and IIA in response to IFN-γ is much dependent on cell type, and (b) the regulation of PLA2 type IID in human macrophages is clearly different from that of PLA2 type IVA. (c) PLA2 IVA is probably under control of both NF-κB and IFN-γ-responsive elements (GRE) or IFN-γ-activating sites (GAS). The possibility that PLA2 IID is involved in cytokine-mediated inflammation in the nasal mucosa is inferred, as is the potential role of PLA2 IID in the host defense against LPS-containing bacteria.

1 - 13 of 13
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