Ohguchi M, Yamato K, Ishihara Y, Koide M, Ueda N, Okahashi N, Noguchi T, Kizaki M, Ikeda Y, Sugino H, Nisihara T
Department of Oral Science, National Institute of Infectious Diseases, Tokyo, Japan.
J Interferon Cytokine Res. 1998 Jul;18(7):491-8. doi: 10.1089/jir.1998.18.491.
Activin A, a member of the transforming growth factor-beta (TGF-beta) family, is produced by a variety of cells and implicated in the regulation of the reproductive endocrine system, mesoderm induction, and erythropoiesis. In the present study, we showed that activin A inhibited the production of interleukin-1beta (IL-1beta), a potent proinflammatory cytokine, and enhanced the production of IL-1 receptor antagonist (IL-1ra), in activated THP-1 and U-937 human monocytic cells, resulting in the reduction of IL-1 biologic activity. Northern blot analysis revealed that activin A had no effect on mRNA accumulation of IL-1beta and IL-1ra, indicating that activin A regulates IL-1beta and IL-1ra production at a posttranscriptional level. As it is well known that an inactive precursor form of IL-1beta (pro-IL-1beta) is converted to an active mature form (mature IL-1beta), we examined the expression levels of pro-IL-1beta and mature IL-1beta by immunoblot analysis. Although activin A inhibited the production of mature IL-1beta in activated U-937 cells, the relative protein expression of pro-IL-1beta was unaltered by activin A, suggesting that activin A inhibits IL-1beta production by blocking proteolytic conversion of pro-IL-1beta into mature IL-1beta. Taken together, these findings suggest that activin A may function as an anti-inflammatory cytokine by modulating mature IL-1beta and IL-1ra production in inflammatory sites.
激活素A是转化生长因子-β（TGF-β）家族的成员之一，由多种细胞产生，参与生殖内分泌系统的调节、中胚层诱导和红细胞生成。在本研究中，我们发现激活素A可抑制活化的THP-1和U-937人单核细胞中白细胞介素-1β（IL-1β，一种强效促炎细胞因子）的产生，并增强IL-1受体拮抗剂（IL-1ra）的产生，从而导致IL-1生物活性降低。Northern印迹分析显示，激活素A对IL-1β和IL-1ra的mRNA积累没有影响，这表明激活素A在转录后水平调节IL-1β和IL-1ra的产生。众所周知，IL-1β的无活性前体形式（前IL-1β）会转化为活性成熟形式（成熟IL-1β），因此我们通过免疫印迹分析检测了前IL-1β和成熟IL-1β的表达水平。虽然激活素A抑制了活化的U-937细胞中成熟IL-1β的产生，但前IL-1β的相对蛋白表达不受激活素A的影响，这表明激活素A通过阻断前IL-1β向成熟IL-1β的蛋白水解转化来抑制IL-1β的产生。综上所述，这些发现表明激活素A可能通过调节炎症部位成熟IL-1β和IL-1ra的产生而发挥抗炎细胞因子的作用。
