Emodin attenuates silica-induced lung injury by inhibition of inflammation, apoptosis and epithelial-mesenchymal transition

Silicosis is a fatal pulmonary disease caused by the inhalation of silica dust, and characterized by inflammation and fibrosis of the lung, with no effective treatment to date. Here we investigate the effect of emodin, an anthraquinone derivative isolated from rhubarb using a mouse silicosis model and in vitro cultured human macrophages and alveolar epithelial cells. Results from histological examination indicated that emodin reduced the degree of alveolitis and fibrosis in the lungs of mice exposed to silica particles. We also demonstrated that emodin effectively inhibited the phosphorylation of Smad3 and NF-kappa B and reduced the levels of inflammatory factors in the lung tissue of mice treated with silica particles. In addition, we found that emodin inhibited apoptosis and demonstrated an anti-fibrotic effect by down-regulating the pro-apoptotic protein Bax and up regulating the anti-apoptotic protein Bcl-2. Furthermore, emodin increased E-cadherin levels, reduced the expression of Vimentin, alpha-SMA and Col-I, as well as pro-inflammatory factors TGF-beta 1, TNF-alpha and IL-1 beta in vivo and in vitro. These results suggested that emodin can regulate epithelial-mesenchymal transition (EMT) through the inhibition of the TGF-beta 1/Smad3 signaling pathway and the NF-kappa B signaling pathway to prevent alveolar inflammation and apoptotic process. Overall, this study showed that emodin can alleviate pulmonary fibrosis in silicosis through regulating the inflammatory response and fibrotic process at multiple levels.