The roles of activin A and its binding protein, follistatin, in inflammation and tissue repair

• Published in: Molecular and cellular endocrinology 2012-08, Vol.359 (1-2), p.101-106
• Main Authors: de Kretser, David M., O’Hehir, Robyn E., Hardy, Charles L., Hedger, Mark P.
• Format: Article
• Language: English
• Subjects: Activation; Activin; Activins - metabolism; Activins - physiology; Animals; anti-inflammatory activity; antibody formation; Binding; blood serum; Cascades; Cellular; Cytokines; death; Fibrosis; Follistatin; Follistatin - metabolism; Follistatin - physiology; Humans; Immunomodulation; Infection markers in blood; Inflammation; Inflammation - metabolism; laboratory animals; lipopolysaccharides; Lymphocytes - immunology; Lymphocytes - metabolism; Lymphocytes - physiology; macrophages; Modulation; mortality; patients; pretreatment; Proteins; septicemia; signal transduction; T-lymphocytes; TGF-beta Superfamily Proteins - metabolism; TGF-beta Superfamily Proteins - physiology; tissue repair; Toll-like receptor 4; Wound Healing
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2011.10.009

Activin A, a member of the transforming growth factor-β superfamily of cytokines, is a critical controller of inflammation, immunity and fibrosis. It is rapidly released into the blood following a lipopolysaccharide challenge in experimental animals, through activation of the Toll-like receptor 4 signalling pathway. Blocking activin action by pre-treatment with its binding protein, follistatin, modifies the inflammatory cytokine cascade, and reduces the severity of the subsequent inflammatory response and mortality. Likewise, high serum levels of activin A are predictive of death in patients with septicaemia. However, activin A has complex immunomodulatory actions. It is produced by inflammatory macrophages, but can regulate either pro- or anti-inflammatory responses in these cells, depending on their prior activation status. Activin A is also produced by Th2 cells, and stimulates antibody production by B cells and the development of regulatory T cells. Production of activin A during inflammatory responses stimulates fibrosis and tissue remodelling, and follistatin inhibits these actions of activin A. The modulation of activin by follistatin may represent an important therapeutic target for the modulation and amelioration of inflammatory and fibrotic disorders.