Group II phospholipase A(2) as an autocrine growth factor mediating interleukin-1 action on mesangial cells

The proliferation of mesangial cells plays a central role in the progression of glomerulonephritis. We studied the role of group II phospholipase A(2) in interleukin-1-stimulated proliferation of mesangial cells. Cultured rat mesangial cells secreted 5.3 units group II phospholipase A(2)/24 h per 10(5) cells in response to stimulation of 200 U/ml of interleukin-1. Northern hybridization analysis showed that mRNA for group II phospholipase A(2) was induced by exogenously added group II phospholipase A(2) (15 U/ml) as well as interleukin-1. The pretreatment of quiescent mesangial cells with interleukin-1 augmented [H-3]thymidine incorporation caused by platelet derived growth factor. Exogenous group II phospholipase A? (5-36 U/ml) purified homogeneously from rat spleen also increased [H-3]thymidine incorporation by platelet derived growth factor-stimulated mesangial cells in a dose dependent manner (36 U/ml phospholipase A(2); 1.9-fold). The stimulatory effect of interleukin-l on DNA synthesis of mesangial cells was specifically blunted by immunoglobulin raised against group II phospholipase A(2). Group II phospholipase A(2) (16 U/ml) amplified a platelet derived growth factor-stimulated increase in the mesangial cell number by 1.5-fold. Among the products of the phospholipase A(2)-catalyzed reaction, lysophospholipids including lysophosphatidylcholine, lysophosphatidylethanolamine and lysophosphatidic acid, but not fatty acids, mimicked the stimulatory effect of interleukin-l and phospholipase A(2). These results suggest that group II phospholipase A(2) acts as a signaling molecule that mediates interleukin-1-induced growth of rat mesangial cells through yielding lysophospholipids.