The European respiratory journal

Role of activin-A in cigarette smoke-induced inflammation and COPD.

PMID 24232707


Activin-A is a pleiotropic cytokine belonging to the transforming growth factor-β superfamily and has been implicated in asthma and pulmonary fibrosis. However, the role of activin-A and its endogenous inhibitor, follistatin, in the pathogenesis of chronic obstructive pulmonary disease (COPD) is unknown. We first quantified activin-A and follistatin in the lungs of air- or cigarette smoke-exposed mice and in the lungs of patients with COPD by immunohistochemistry, ELISA and quantitative real-time PCR. We subsequently studied the effect of cigarette smoke on primary human bronchial epithelial cells in vitro. Next, activin-A signalling was antagonised in vivo by administration of follistatin in mice exposed to air or cigarette smoke for 4 weeks. Protein levels of activin-A were increased in the airway epithelium of patients with COPD compared with never-smokers and smokers. Cigarette smoke-exposed human bronchial epithelial cells expressed higher levels of activin-A and lower levels of follistatin. Both mRNA and protein levels of activin-A were increased in the lungs of cigarette smoke-exposed mice, whereas follistatin levels were reduced upon cigarette smoke exposure. Importantly, administration of follistatin attenuated the cigarette smoke-induced increase of inflammatory cells and mediators in the bronchoalveolar lavage fluid in mice. These results suggest that an imbalance between activin-A and follistatin contributes to the pathogenesis of cigarette smoke-induced inflammation and COPD.