Activin A regulates the production of mature interleukin-1beta and interleukin-1 receptor antagonist in human monocytic cells.

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.