Production of activin A and its roles in inflammation and hematopoiesis

Activin A, a member of the transforming growth factor beta (TGF-beta) superfamily, is a protein consisting of two homodimeric beta A subunits. It was originally isolated from follicular fluid as a factor stimulating the release of follicle-stimulating hormone from the pituitary gland. Increasing evidence suggests that activin A is broadly distributed and regulates multiple functions in various biological systems by autocrine/paracrine mechanisms. In this review, we discuss the effects of activin A on hematopoiesis, especially the enhancement of erythropoiesis, and the production of activin A within the bone marrow microenvironment and in peripheral blood monocytes. The regulatory control of activin A expression by its 5' promoter region is also discussed. Furthermore, we consider that the expression of activin A is modulated by different agents, including proinflammatory cytokines, glucocorticoids and retinoic acid, suggesting new roles for activin A in inflammation reactions. Recently, this role in inflammation was further strengthened by the findings that activin A expression is elevated in inflammatory arthropathies, is regulated by inflammation-associated cytokines in synoviocyte and articular chondrocyte cultures, and is able to counteract many of the interleukin-6 (IL-6)-induced biological activities. Therefore it is likely that activin A may also act as a paracrine/autocrine moderator in diverse functions, including host defenses.