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Group II phospholipase A2 activates mitogen-activated protein kinase in cultured rat mesangial cells
1First Department of Medicine, Osaka University School of Medicine, Japan.
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-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.
Insights
Group II phospholipase A2 (PLA2) is involved in kidney inflammation. Interleukin-1 (IL-1) stimulates mesangial cells, and secreted PLA2 mediates a key signaling pathway, MAP kinase activation.
Area of Science:
- Nephrology
- Immunology
- Cell Biology
Background:
- Group II phospholipase A2 (PLA2) is implicated in inflammatory diseases like glomerulonephritis.
- Elevated urinary PLA2 levels are observed in mesangial proliferative glomerulonephritis patients.
- Interleukin-1 (IL-1) promotes mesangial cell proliferation via PLA2, stimulated by platelet-derived growth factor.
Purpose of the Study:
- To elucidate the signal transduction mechanism of group II PLA2 in mesangial cells.
- To investigate the role of secreted group II PLA2 in IL-1-induced cellular responses.
Main Methods:
- Treatment of mesangial cells with group II PLA2 and IL-1 beta.
- Assessment of mitogen-activated protein (MAP) kinase activation.
- Inhibition studies using a specific antibody against group II PLA2.
Main Results:
- Group II PLA2 rapidly activated MAP kinase in mesangial cells.
- IL-1 beta induced a biphasic MAP kinase activation.
- The late phase of IL-1-induced MAP kinase activation correlated with PLA2 secretion and was blocked by anti-PLA2 antibody.
Conclusions:
- Secreted group II PLA2 plays a significant role in the late phase of IL-1-induced MAP kinase activation in mesangial cells.
- This pathway is a potential therapeutic target for glomerulonephritis and other inflammatory kidney diseases.