Group II phospholipase A2 activates mitogen‐activated protein kinase in cultured rat mesangial cells

Group II phospholipase A2 (PLA2) is a mediator of inflammation in various disease including glomerulonephritis. We recently found that urinary excretion of PLA2 was increased in patients with mesangial proliferative glomerulonephritis and that interleukin-1 (IL-1) enhanced platelet derived growth factor-stimulated mesangial cell proliferation through the action of group II PLA2 secreted in response to IL-1 stimuli. Here we report signal transducing mechanism through group II PLA2 in mesangial cells. Group II PLA2 (1-15 U/ml) rapidly activated mitogen-activated protein (MAP) kinase. IL-1 beta activated MAP kinase in two phases and the slow activation in the late phase, proceeding in parallel with increased group II PLA2 secretion elicited by IL-1 treatment, was inhibited by the specific antibody raised against group II PLA2. This suggests that the late phase activation of IL-1-induced MAP kinase was mediated, at least in part, by secreted group II PLA2.