Effects of activin A on IgE synthesis and cytokine production by human peripheral mononuclear cells

Abstract

SUMMARYActivin A not oniy stimulates the synthesis and release of pituitary follicie-stimuiating honnone. but exerts various effects on haematopoietic cetis. embryos, and fibroblasts. In the present study we have examined effects of activin A on lgH synthesis and cytokine production by peripheral blood mononuciear ceiis (PBMt") in normai humans. When PBMC were cultuted in the prcsenee of lL-4. activin A significantiy augmented IgE production induced by IL-4. Activin A did not atlect, however, IgE production from highiy purified B ceiis when they were stimuiated with anti-CD4() MoAb and IL-4. The fact that in the iatter condition IgE synthesis was T ceii-and monocytc-indcpcndent indicated that activin A does not directiy inlluence B ceiis for IgE synthesis. Rather, production as weii as gene expression of IL-6, which is known to enhance IgE syntiiesis by puriiied monoeytes. was induced by activin A aione. In addition, activin A induced other monokines such as lL-l and tutnour necrosis factor (TNF)-a from monoeytes. In contrast, activin A neither induced nor augmented the production of TNF-/i or interferon-gamma (IFN-y). both of which arc known to be cxciusiveiy generated by Tceils. These data indicate that activin A piays a certain role in piiysioiogicat functions for monocyles in normal humans.

Acute regulation of activin A and its binding protein, follistatin, in serum and tissues following lipopolysaccharide treatment of adult male mice

“…This effect of blocking activin A by follistatin was consistent with studies that have shown that activin A stimulates production of these cytokines, and other proinflammatory genes, in human, rat, and mouse mononuclear phagocytes in vitro (22,23,42). These data indicate a crucial role for activin A, and, consequently, for endogenous follistatin, in controlling the severity of acute inflammation and its subsequent actions.…”

Activin A is a critical component of the inflammatory response, and its binding protein, follistatin, reduces mortality in endotoxemia

“…Activin stimulates I-B activation, nuclear translocation of NF-B, and phosphorylation of ERK1/2 and p38 MAP kinase in murine BMMs under basal conditions and when stimulated with the receptor activator of NF-B ligand and/or colony-stimulating factor-1 (23,24). Accordingly, activin has been found to stimulate the production of IL-1␤ and TNF by rat BMMs (19) and IL-1␤, IL-6, and TNF by human monocytes and peripheral blood mononuclear cells (25). However, activin also has been shown to inhibit the conversion of the IL-1␤ precursor to its secreted bioactive form, presumably by inhibiting caspase-1 activity (26), and to inhibit secretion of IL-6 by human endometrial epithelial cells (27) and rat thymocytes (28).…”

The bright and the dark sides of activin in wound healing and cancer

“…A proinflammatory activity is suggested by the pro-migratory effect of activin on monocytes (Petraglia et al, 1991). Furthermore, activin stimulated the production of pro-inflammatory cytokines in human peripheral blood mononuclear cells (Yamashita et al, 1993) and in rat bone-marrow-derived macrophages (Nüsing and Barsig, 1999). However, anti-inflammatory effects of activin have also been demonstrated.…”