Cytokine regulation of group II phospholipase A2 expression in glomerular mesangial cells.
Phospholipase A2 (PLA2) is believed to play an essential role in inflammatory processes by releasing arachidonic acid from membrane phospholipids for synthesis of important lipid mediators, such as prostaglandins, leukotrienes and platelet activating factor. We have used glomerular mesangial cells as a model system to study the regulation of PLA2 under inflammatory conditions. Potent pro-inflammatory cytokines, such as interleukin 1 (IL-1) and tumour necrosis factor alpha (TNF alpha), as well as agents that increase cellular cAMP levels have been found to increase Group II PLA2 gene expression in a time- and dose-dependent manner. In all cases cytokine-induced synthesis of PLA2 occurred in parallel with cytokine-stimulated prostaglandin (PG) E2 synthesis. Three important classes of compounds that potently antagonise the stimulatory effect of IL-1, TNF alpha and cAMP on Group II PLA2 expression in mesangial cells have been identified, namely, glucocorticoids, transforming growth factors (TGF) type-beta and platelet-derived growth factor (PDGF). Those agents may act sequentially to protect the kidney from damage resulting from cytokine-stimulated mediator release and the subsequent inflammatory reactions.
Department of Pharmacology, University of Basle, Switzerland.
J
J
Pfeilschifter
H
H
Mühl
W
W
Pignat
F
F
Märki
H
H
van den Bosch
D000818:Animals; D002999:Clone Cells; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005920:Glomerular Mesangium / Q000166:cytology / Q000201:enzymology*; D005938:Glucocorticoids / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D010741:Phospholipases A / Q000096:biosynthesis*; D054467:Phospholipases A2; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D005938:Glucocorticoids; D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D014409:Tumor Necrosis Factor-alpha; D005576:Colforsin; D000242:Cyclic AMP; D010741:Phospholipases A; D054467:Phospholipases A2