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.
Yu
J
J
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA.
Dolter
K E
KE
D028341:Activins; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology; D006410:Hematopoiesis; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007265:Inhibins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015850:Interleukin-6 / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D000093242:Interleukin-6 Inhibitors
D028341:Activins; D016207:Cytokines; D005938:Glucocorticoids; D007265:Inhibins; D015850:Interleukin-6; D014212:Tretinoin; D000093242:Interleukin-6 Inhibitors