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Expression of members of the phospholipase A2 family of enzymes in human nasal mucosa
Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
2001 (English)In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 18, no 1, 130-138 p.Article in journal (Refereed) 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.

Place, publisher, year, edition, pages
2001. Vol. 18, no 1, 130-138 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-26015DOI: 10.1183/09031936.01.00054701Local ID: 10468OAI: oai:DiVA.org:liu-26015DiVA: diva2:246563
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13
In thesis
1. Phospholipase A2 expression in the human nasal mucosa
Open this publication in new window or tab >>Phospholipase A2 expression in the human nasal mucosa
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
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.

Place, publisher, year, edition, pages
Linköping: Linköping University, 2004. 100 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 864
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-22294 (URN)1480 (Local ID)91-7373-838-7 (ISBN)1480 (Archive number)1480 (OAI)
Public defence
2004-11-11, Aulan, Hälsans hus, Hälsouniversitetet, Linköping, 09:00 (Swedish)
Opponent
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-10-29Bibliographically approved
2. Phospholipase A2 expression in the human nasal mucosa
Open this publication in new window or tab >>Phospholipase A2 expression in the human nasal mucosa
2002 (English)Licentiate thesis, comprehensive summary (Other academic)
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.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2002. 48 p.
Series
Linköping Studies in Health Sciences. Thesis, ISSN 1100-6013 ; 54
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-26681 (URN)11248 (Local ID)91-7373-175-7 (ISBN)11248 (Archive number)11248 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2013-07-11

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Lindbom, JohnLjungman, AndersLindahl, MatsTagesson, Christer

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