RESUMO
Objective To evaluate the ameliorative effect of telmisartan on the inflammatory reaction induced by lipopolysaccharide(LPS) in microglia cells and investigate its effect on modulation of activated microglia phenotype transformation by activation of the peroxisome proliferator-activated receptor γ (PPARγ) accordingly. Methods The PPARγ agonistic activity of telmisartan was explored using PPARγ-responsive element- lucifarase reporter assay ,and inflammatory model was established through LPS-induced microglia cells. The mice microglia cells (BV-2 microglia cell line) were treated in the presence of telmisartan ranging from 0.1 to 10 μmol/L or in the presence of 1 mol/L telmisartan with 10 μmol/L GW9662, the specific PPARγ antagonist. The contents of tumor necrosis factor-alpha (TNF-α ) in cell supernatants were analyzed by ELISA; the mRNA expression level of M1 phenotype markers CD16, CD11b and iNOS as well as M2 phenotype marker IL-10 were evaluated using the real-time quantitative PCR. Results Compared with control group, telmisartan could concentration-dependently activate the PPARγ ranging from 0.1 to 10 μmol/L and the relative lucifarase activity induced by telmisartan was 1.29, 1.36 and 1.45 folds (P<0.01), respectively; in the inflammatory model of BV-2 cells induced by LPS, compared with control group, the content of TNF-α in cell supernatants significantly increased (P<0.01) and the mRNA expression level of M1 phenotype microglia markers CD16, CD11b and iNOS was significantly up-regulated (P<0.05) in LPS group; compared with LPS group, telmisartan could concentration-dependently decreased the content of TNF-α in cell supernatants arranging from 0.1 to 10 mol/L (P<0.05); 10 mol/L telmisartan could significantly down-regulated the mRNA expression level of M1 phenotype microglia markers CD16, CD11b and iNOS (P<0.01, P<0.05 and P<0.05) ; additionally, 0.1 μmol/L telmisartan could significantly up-regulated the mRNA expression level of M2 phenotype microglia marker IL-10 (P<0.05); compared with 1 mol/L telmisartan treated group, the mRNA expression level of CD16 was significantly up-regulated by specific PPARγ antagonist GW9662 (P<0.05). Conclusion Telmisartan could markedly reduce the release of TNF-α in LPS-induced activated microglia cells; the mechanism is associated with modulating the transformation of M1/M2 microglia phenotype by the activation of PPARγ.
