激活素A对小鼠巨噬细胞分泌IL-1β的影响

Effects of activin A on IL-1β secretion by the murine macrophages

目的:探讨激活素A对小鼠腹腔巨噬细胞活性的调节作用及其机制。方法:免疫组化观察激活素ⅡA型受体(ActRⅡA)在巨噬细胞上的表达,ELISA法检测小鼠腹腔巨噬细胞培养上清中IL-1β分泌水平,采用RT-PCR检测小鼠腹腔巨噬细胞IL-1βmRNA、ActRⅡAmRNA及激活素受体相互作用蛋白2(ActRIP2)mRNA的表达。结果:激活素A可以促进原代培养小鼠腹腔巨噬细胞分泌IL-1β及IL-1βmRNA表达,并呈剂量依赖关系;激活素A对LPS活化的小鼠原代培养腹腔巨噬细胞分泌IL-1β及IL-1βmRNA的表达具有抑制作用,并呈剂量依赖关系。免疫组化染色证实ActRⅡA在巨噬细胞中高表达,激活素A对巨噬细胞表达ActRⅡAmRNA具有促进作用,采用抗ActRⅡA抗体可以阻断激活素A促进IL-1βmRNA表达作用,进一步检测表明激活素作用后ActRIP2mRNA表达亦增加。结论:激活素与LPS比较可能是IL-1分泌的弱激动剂,激活素单独应用显示刺激IL-1分泌作用,而与LPS共同作用,则呈现抑制LPS强刺激作用;激活素可能通过ActRIIA-ActRIP2受体信号传导途径,调控巨噬细胞IL-1β分泌与合成。

Objectlve：To investigate the effect and mechanism of acrid-in A on activities of the routine peritoneal macrophages.Methotis：To observe the expression of ActRⅡA on macrophages by immunocytoehemistry, to examine the secretion of IL-1β in the supematant of cultured macrophages by ELISA and to analyze the expression of IL-1β, ActRⅡA and ActRIP2 mRNA in the macrophages by RT-PCR.Resuits：The results showed that activin A stimulated secretion of IL-1β and the expression of IL-1β mRNA in non-activated macrophages in a dose-dependem manner. In contrast, activin A in the same concentration inhibited the secretion of IL-1β and the expression of IL-1β mRNA in LPS-aetivated macrophages in a dose-dependent manner. ActR Ⅱ A was highly expressed on the surface of the macrophages, and aetivin A upregulated the ActR Ⅱ A mRNA expression in macrophages. Anti-ActR ⅡA antibody can block the expression of IL-1β mRNA in the maerophages stimulated by activin A. RT-PCR analysis also revealed that activin A enhanced the ActRIP2 mRNA expression. Conclusion： Activin A may be one kind of weak activators compared with LPS, stimulating secretion of IL-1β of macrophages alone, whereas, acfivin A inhibits secretion of IL-1β of macrophages activated by LPS. Aefivin A may regulate secretion and production of IL-1β through ActRⅡA-AetRIP2 signal pathway.