Shp-2/NF-κB Pathway Mediates the Inhibition of Lipoxin A_4 on IL-1β-induced Synthesis of IL-6 in Glomerular Mesangial Cells

摘要

Objective: To examine whether lipoxin A_4 (LXA_4) has an antagonistic effect on IL-1β-induced synthesis of IL-6 in glomerular mesangial cells, and to explore the molecular mechanisms of signal pathway in LXA_4 actions. Methods: The glomerular mesangial cells of rat were cultured and treated with EL-1β, with or without preincu-bation with LXA_4 at different concentrations. The amount of IL-6 in the supernatant of cells was analyzed by enzyme-linked immunosorbent assay(ELISA). The expressions of mRNA of IL-6 were determined by RT-PCR. The expressions of Src homology 2(SH_2) containing protein-tyrosine phosphatase 2(Shp-2) were assessed by immunoprecipitation and immunoblotting. Activities of DNA-binding of nuclear factor-kappa B(NF-κB) were measured by electrophoretic mobility shift assay(EMSA). Results: IL-1β-stimulated secretion of protein and expression of mRNA of IL-6 in mesangial cells were inhibited by LXA_4 in a dose-dependent manner. LXA_4 antagonizes the phosphorylation of Shp-2 and activities of NF-κB induced by IL-1β. Conclusion: LXA_4 antagonists IL-1β-induced synthesis of IL-6 in glomerular mesangial cells through the mechanism of Shp-2/NF-κB pathway-dependent signal transduction.