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Lipopolysaccharide- and ß-glucan-stimulated macrophages upregulate cytolosic phospholipase A2 IVC in nasal epithelial cells: role of TNF-α
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.
(English)Manuscript (preprint) (Other academic)
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.

National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-84953OAI: oai:DiVA.org:liu-84953DiVA: diva2:563152
Available from: 2012-10-29 Created: 2012-10-29 Last updated: 2012-10-29
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

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Lindbom, JohnLjungman, Anders G.Tagesson, Christer

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