Increased gene expression of novel cytosolic and secretory phospholipase A(2) types in human airway epithelial cells induced by tumor necrosis factor-alpha and IFN-gamma.
Phospholipase A(2) (PLA(2)) is a growing family of enzymes that may play a major role in inflammation. We investigated the effect of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) on the gene expression of 19 different PLA(2) 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-alpha or IFN-gamma for different lengths of time (1, 4, 18, and 48 h), and the mRNA levels of the different PLA(2) types were determined by reverse transcriptase-PCR (RT-PCR) and normalized to those of the housekeeping gene, GAPDH. In both cell lines, TNF-alpha increased the expression of PLA(2) IVA and IVC, and IFN-gamma increased the expression of PLA(2) IIA and IID. No influence on the gene expression of PLA(2)-activating protein (PLAP) was noted on cytokine stimulation. These findings indicate that TNF-alpha and IFN-gamma induce gene expression of two novel cytosolic and secretory PLA(2) types (IVC and IID, respectively) in human airway epithelial cells. The possibility that these PLA(2) types are involved in cytokine-mediated inflammation in the respiratory tract is inferred.
Lindbom
John
J
Department of Molecular and Clinical Medicine, Division of Occupational and Environmental Medicine, Faculty of Health Sciences, University of Linköping, S-581 85 Linköping, Sweden. Johli@ihm.liu.se
Ljungman
Anders G
AG
Lindahl
Mats
M
Tagesson
Christer
C
D001980:Bronchi / Q000187:drug effects / Q000201:enzymology*; D003600:Cytosol / Q000201:enzymology*; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D054501:Group II Phospholipases A2; D054513:Group IV Phospholipases A2; D006801:Humans; D007249:Inflammation / Q000201:enzymology; D007371:Interferon-gamma / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D009297:Nasal Mucosa / Q000187:drug effects / Q000201:enzymology*; D010741:Phospholipases A / Q000096:biosynthesis / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007527:Isoenzymes; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D007371:Interferon-gamma; C472331:PLA2G4C protein, human; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054513:Group IV Phospholipases A2