Baccatin III ameliorates bleomycin-induced pulmonary fibrosis via suppression of TGF-β1 production and TGF-β1-induced fibroblast differentiation.

Yunjuan Nie, Dan Zhang, Feng Qian, Yaxian Wu

International immunopharmacology 2019 Sep

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Idiopathic pulmonary fibrosis (IPF) is a progressive and generally lethal lung disease with a high mortality rate. Current therapeutic drugs exhibit limited efficacy but severe adverse effects. Paclitaxel has been identified to exert both anti-inflammatory and anti-fibrosis activity. Baccatin III (BAC), an important precursor of paclitaxel, has been identified as exhibiting immunomodulatory activity with decisively lower toxicity. However, its effects on pulmonary fibrosis remain unknown. In this study, the role of BAC in bleomycin (BLM)-induced pulmonary fibrosis and inflammation in mice was investigated in addition to elucidation of its mechanism of action. Our results demonstrated that administration of BAC in a dose-dependent manner reduced inflammatory infiltration, secretion of the pro-fibrotic mediator TGF-β1 and deposition of collagen and other components of the extracellular matrix (ECM), including alpha smooth muscle actin (α-SMA) and fibronectin. Administration of BAC to treat isolated macrophages stimulated with IL-13, known to activate macrophages, the principal source of TGF-β1, resulted in markedly reduced TGF-β1 expression from macrophages. The AKT/STAT6 signaling pathway was shown to be involved in this process. In addition, we have provided in vitro evidence that BAC inhibits TGF-β1-induced fibroblast differentiation via the Smad2/3 signaling pathway. Furthermore, intratracheal injection of rTGF-β1 significantly exacerbated the degree of fibrosis which was down-regulated by treatment with BAC. Taken together, our data suggest that BAC exerts a protective effect against lung fibrosis and may serve as a potential therapeutic strategy for IPF. Copyright © 2019 Elsevier B.V. All rights reserved.

Citation

Yunjuan Nie, Dan Zhang, Feng Qian, Yaxian Wu. Baccatin III ameliorates bleomycin-induced pulmonary fibrosis via suppression of TGF-β1 production and TGF-β1-induced fibroblast differentiation. International immunopharmacology. 2019 Sep;74:105696