Cytokine regulation of Group II phospholipase A2 expression in glomerular mesangial cells
- 25 Downloads
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 α (TNFα), 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, TNFα and cAMP on Group II PLA2 expression in mesangial cells have been identified, namely, glucocorticoids, transforming growth factors (TGF) type-β 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.
Key wordsPhospholipase A2 Mesangial cell Cytokines interleukin 1 tumour necrosis factor α transforming growth factorβ platelet-derived growth factor glucocorticoids
- 12.Mühl H, Geiger T, Pignat W, Märki F, Van den Bosch H, Cerletti N, Cox D, McMaster G, Vosbeck K, Pfeilschifter J (1992) Transforming growth factors type-β and dexamethasone attenuate group II phospholipase A2 gene expression by interleukin-1 and forskolin in rat mesangial cells. FEBS Lett 301:190–194PubMedGoogle Scholar
- 14.Pfeilschifter J, Pignat W, Leighton J, Märki F, Vosbeck K, Alkan S (1990) Transforming growth factorβ 2 differentially modulates interleukin-1β- and tumour-necrosis-factor-α-stimulated phospholipase A2 and prostaglandin E2 synthesis in rat renal mesangial cells. Biochem J 270:269–271PubMedGoogle Scholar