S632A3通过抑制GSK-3β活性促进LPS诱导巨噬细胞产生IFN-β

S632A3 promotes LPS-induced IFN-β production through inhibiting the activation of GSK-3β

LPS刺激巨噬细胞产生IFN-β在抵御外来病原微生物的免疫反应中发挥重要作用。本研究探讨新抗生素S632A3促进LPS诱导巨噬细胞产生IFN-β及其分子机制。采用实时定量PCR检测mRNA含量,ELISA检测细胞因子含量,激酶分析检测GSK-3β活性,Western blotting检测蛋白磷酸化水平。结果表明:S632A3可显著促进LPS诱导的巨噬细胞产生IFN-β,其分子机制是抑制细胞内GSK-3β活性,降低转录因子c-Jun苏氨酸239位点的磷酸化并增加c-Jun稳定性。结果提示,S632A3是一个新的抗炎先导化合物,通过抑制GSK-3β活性促进LPS诱导巨噬细胞产生IFN-β。

LPS stimulation of macrophages production of IFN-β plays a key role in innate immunity defending the microbial invasion. In this study, the effect of S632A3 promoting LPS-induced IFN- β production and the underlying mechanism were investigated, mRNA level was measured by real-time PCR, cytokine production was determined by ELISA, GSK-3β activity was investigated by kinase assay, protein phosphorylation and expression were evaluated by Western blotting. The results revealed that S632A3 significantly augmented IFN-β production by LPS-stimulated macrophages. S632A3 inhibition of the activation of GSK-3 β, reduced the threonine 239 phosphorylation of transcription factor c-Jun but increased the total level of c-Jun in LPS- stimulated macrophages. Moreover, small interfering RNA-mediated knockdown of c-Jun level abrogated the ability of S632A3 to augment IFN-β. The study thus demonstrates S632A3 being a new anti-inflammation lead compound and provides a molecular mechanism by which S632A3 promoted LPS-induced IFN-β production in macrophages through inhibiting the activation of GSK-3 ft.