ACTIVIN A REGULATES THE PRODUCTION OF MATURE INTERLEUKIN-1-BETA 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 regula tion of the reproductive endocrine system, mesoderm induction, and ery thropoiesis, In the present study, we showed that activin A inhibited the production of interleukin-1 beta (IL-1 beta), a potent proinflamma tory cytokine, and enhanced the production of IL-1 receptor antagonist (IL-1ra), in activated THP-1 and U-937 human monocytic cells, resulti ng in the reduction of IL-1 biologic activity. Northern blot analysis revealed that activin A had no effect on mRNA accumulation of IL-1 bet a and IL-1ra, indicating that activin A regulates IL-1 beta and IL-1ra production at a posttranscriptional level. As it is well known that a n inactive precursor form of IL-1 beta (pro-IL-1 beta) is converted to an active mature form (mature IL-1 beta), we examined the expression levels of pro-IL-1 beta and mature IL-1 beta by immunoblot analysis, A lthough activin A inhibited the production of mature IL-1 beta in acti vated U-937 cells, the relative protein expression of pro-IL-1 beta wa s unaltered by activin A, suggesting that activin A inhibits IL-1P pro duction by blocking proteolytic conversion of pro-IL-1 beta into matur e IL-1 beta. Taken together, these findings suggest that activin A may function as an anti-inflammatory cytokine by modulating mature IL-1 b eta and IL-1ra production in inflammatory sites.