The Molecular Mechanism Of LPS-induced Activation In Microglia

Objective:To investigate the expression of the proinflammatory cytokines and chemokines, TNF-a, IL-6, NO, MCP-1and RANTES, the expression of the TNF-α, IL-6, iNOS mRNA, and the levels of phospho-p38MAPK, JNK, ERK in the microglial cells stimulated with LPS.Methods:The microglial cells from10Wistar rats aged1-2days were cultured in MEM supplemented with10%fetal bovine serum. The microglial cells were divided into two groups: control group and group stimulated with LPS. The expression of TNF-a, IL-6, MCP-1and RANTES were measured by enzyme linked immuno-sorbent assay(ELISA). The expression of nitric oxide (NO) was assessed by Griess reaction. The expression of TNF-a, IL-6and iNOS mRNA in both groups were assessed by RT-PCR analysis. The levels of phospho-p38MAPK, JNK and ERK were determined by Western blotting method.Results:Compared with those in the control group TNF-a, IL-6, NO, MCP-1and RANTES contents were higher in the LPS group(P<0.05). It was also found that the expression of TNF-α, IL-6and iNOS mRNA in groups treated with LPS were higher than that in the control group(P<0.05). The levels of P-p38, P-JNK and P-ERK were higher in the LPS group than in the control group(P<0.05).Conclusions:LPS could activate the microglial cells. The microglial cells treated with LPS secreted large amounts of the proinflammatory cytokines and chemokines, TNF-α, IL-6, NO, MCP-1and RANTES. LPS could enhance the expression of phosphorylated p38, JNK and ERK proteins, meanwhile couse the release of downriver proinflammatory cytokines and chemokines by activation of p38/JNK/ERK MAPK signal transduction pathway in the microglial cells.