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.
Sugiura
T
T
First Department of Medicine, Osaka University School of Medicine, Japan.
Wada
A
A
Itoh
T
T
Tojo
H
H
Okamoto
M
M
Imai
E
E
Kamada
T
T
Ueda
N
N
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000201:enzymology; D004789:Enzyme Activation; D005920:Glomerular Mesangium / Q000201:enzymology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D010741:Phospholipases A / Q000276:immunology / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
D000906:Antibodies; D007375:Interleukin-1; D011994:Recombinant Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010741:Phospholipases A; D054467:Phospholipases A2