liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Phospholipase A2 expression in the human nasal mucosa
Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
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: urn:nbn:se:liu:diva-26681Local ID: 11248ISBN: 91-7373-175-7 (print)OAI: oai:DiVA.org:liu-26681DiVA: diva2:247230
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2013-07-11
List of papers
1. Expression of members of the phospholipase A2 family of enzymes in human nasal mucosa
Open this publication in new window or tab >>Expression of members of the phospholipase A2 family of enzymes in human nasal mucosa
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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-26015 (URN)10.1183/09031936.01.00054701 (DOI)10468 (Local ID)10468 (Archive number)10468 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13
2. Phospholipase A2 mRNA expression in the nasal mucosa of healthy subjects and patients with seasonal allergic rhinitis
Open this publication in new window or tab >>Phospholipase A2 mRNA expression in the nasal mucosa of healthy subjects and patients with seasonal allergic rhinitis
Show others...
2004 (English)In: Rhinology, ISSN 0300-0729, E-ISSN 1996-8604, Vol. 42, no 2, 85-91 p.Article in journal (Refereed) 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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-22328 (URN)15224635 (PubMedID)1528 (Local ID)1528 (Archive number)1528 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
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
Open this publication in new window or tab >>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 (English)In: Journal of Interferon and Cytokine Research, ISSN 1079-9907, E-ISSN 1557-7465, Vol. 22, no 9, 947-955 p.Article in journal (Refereed) 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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-26517 (URN)10.1089/10799900260286650 (DOI)11075 (Local ID)11075 (Archive number)11075 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13

Open Access in DiVA

No full text

Authority records BETA

Lindbom, John

Search in DiVA

By author/editor
Lindbom, John
By organisation
Occupational and Environmental MedicineFaculty of Health Sciences
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 83 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf