GROUP-II PHOSPHOLIPASE A(2) ACTIVATES MITOGEN-ACTIVATED PROTEIN-KINASE IN CULTURED RAT MESANGIAL CELLS

Group II phospholipase A(2) (PL(2)) is a mediator of inflammation in various disease including glomerulonephritis, We recently found that urinary excretion of PLA(2) was increased in patients with mesangial proliferative glomerulonephritis and that interleukin-l (IL-1) enhanced platelet derived growth factor-stimulated mesangial cell proliferation through the action of group II PLA(2) secreted in response to IL-1 stimuli, Here we report signal transducing mechanism through group II PLA(2) in mesangial cells, Group II PLA(2) (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 PLA(2) secretion elicited by IL-1 treatment, was inhibited by the specific antibody raised against group II PLA(2). This suggests that the late phase activation of IL-1-induced MAP kinase was mediated, at least in part, by secreted group LI PLA(2).