Activin A Regulates the Production of Mature Interleukin-1/3 and Interleukin-1 Receptor Antagonist in Human Monocytic Cells

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Abstract
Activin A, a member of the transforming growth factor-β (TGF-β) 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-1β (IL-1β), 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-Iβ and IL-1ra, indicating that activin A regulates IL-1β and IL-1ra production at a posttranscriptional level. As it is well known that an inactive precursor form of IL-1β (pro-IL-1β) is converted to an active mature form (mature IL-1β), we examined the expression levels of pro-IL-Iβ and mature IL-1β by immunoblot analysis. Although activin A inhibited the production of mature IL-1β in activated U-937 cells, the relative protein expression of pro-IL1β was unaltered by activin A, suggesting that activin A inhibits IL-1β production by blocking proteolytic conversion of pro-IL-1β into mature IL-1β. Taken together, these findings suggest that activin A may function as an anti-inflammatory cytokine by modulating mature IL-1β and IL-1ra production in inflammatory sites.