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 v arious disease including glomerulonephritis, We recently found that ur inary excretion of PLA(2) was increased in patients with mesangial pro liferative glomerulonephritis and that interleukin-l (IL-1) enhanced p latelet derived growth factor-stimulated mesangial cell proliferation through the action of group II PLA(2) secreted in response to IL-1 sti muli, 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 i n parallel with increased group II PLA(2) secretion elicited by IL-1 t reatment, was inhibited by the specific antibody raised against group II PLA(2). This suggests that the late phase activation of IL-1-induce d MAP kinase was mediated, at least in part, by secreted group LI PLA( 2).