Cytokine-stimulated secretion of group II phospholipase A2 by rat mesangial cells. Its contribution to arachidonic acid release and prostaglandin synthesis by cultured rat glomerular cells
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Summary
This summary is machine-generated.Pro-inflammatory cytokines stimulate group II phospholipase A2 (PLA2) in mesangial cells, increasing prostaglandin E2 (PGE2) synthesis. Inhibiting group II PLA2 reduces PGE2 production, suggesting its role in glomerular inflammation.
Area Of Science
- Renal Pathophysiology
- Inflammation Biology
- Enzymology
Background
- Pro-inflammatory cytokines like IL-1 and TNF-alpha elevate group II phospholipase A2 (PLA2) in mesangial cells.
- This cytokine-induced PLA2 secretion correlates with increased prostaglandin E2 (PGE2) synthesis.
Purpose Of The Study
- To investigate the role of group II PLA2 in cytokine-stimulated PGE2 production by mesangial cells.
- To determine if extracellular group II PLA2 influences adjacent glomerular cells.
Main Methods
- Utilized a monoclonal antibody to neutralize rat group II PLA2.
- Employed CGP43182, a specific inhibitor of group II PLA2, to assess its effects in vitro and in intact mesangial cells.
- Purified secreted group II PLA2 and tested its effects on mesangial, epithelial, and endothelial cells.
Main Results
- Neutralizing antibody and CGP43182 significantly attenuated IL-1 beta and TNF alpha-stimulated PGE2 production.
- CGP43182 potently inhibited mesangial cell group II PLA2 with low IC50 values.
- Purified group II PLA2 induced arachidonic acid release and PGE2 synthesis in mesangial, epithelial, and endothelial cells.
Conclusions
- Cytokine-induced group II PLA2 secretion by mesangial cells contributes to glomerular PGE2 synthesis.
- Extracellular group II PLA2 can stimulate adjacent glomerular cells, suggesting a role in inflammatory processes.
- Group II PLA2 is a potential therapeutic target in glomerular inflammatory diseases.