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

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Abstract
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‐1β 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.