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Ibrutinib Exacerbates Bleomycin-Induced Pulmonary Fibrosis via Promoting Inflammation

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Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible lung disease with high mortality rate. The etiology is unknown and treatment choices are limited. Thus, there is great interest to investigate novel agents for IPF therapy. Ibrutinib, BTK, and ITK irreversible inhibitor is a FDA-approved small molecule for the clinical therapy of B cell lymphoma. Its role in pulmonary fibrosis remains unknown. In this study, we investigated the anti-fibrotic activity of ibrutinib. Strikingly, ibrutinib did not inhibit but exacerbated bleomycin-induced pulmonary fibrosis by increased epithelial cell apoptosis, and inflammation in the lung. The upregulated TGF-β and EMT transformation also contributes to enhanced myofibroblast differentiation and ECM deposition. Our findings reveal the detrimental effects of ibrutinib against bleomycin-mediated fibrosis and added to the understanding of IPF pathogenesis.

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Funding

Funding

This work was supported by research funding from the National Natural Science Foundation of China (81170015) and Zhejiang Provincial Natural Science Foundation of China (LY15H010001).

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Authors and Affiliations

  1. Department of Respiratory Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310012, China

    Yangyang Gu, Yanfei Yang, Mengdie Qi, Guohua Lu & Hequan Li

  2. Department of Respiratory Diseases, Jiaxing Second Hospital, The Second Affiliated Hospital of Jiaxing University, Jiaxing, 314000, China

    Yangyang Gu

  3. Department of Toxicology, School of Public Health, Zhejiang University, Hangzhou, 310058, China

    Bo Huang & Dajing Xia

  4. School of Public Health, Zhejiang University, Hangzhou, 310058, China

    Dajing Xia

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  1. Yangyang Gu
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Contributions

Author Contributions

Conception and design of research: H.L.; performed the experiments: Y.G., B.H., Y.Y., M.Q., G.L.; analyzed the data and interpreted the results of experiments: Y.G., B.H., H.L.; prepared the figures and drafted the manuscript: Y.G., B.H., Y.Y., M.Q., H.L.; edited and revised the manuscript: Y.G., D.X., H.L

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Correspondence to Hequan Li.

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Gu, Y., Huang, B., Yang, Y. et al. Ibrutinib Exacerbates Bleomycin-Induced Pulmonary Fibrosis via Promoting Inflammation. Inflammation 41, 904–913 (2018). https://doi.org/10.1007/s10753-018-0745-3

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