pci-32765 and Pulmonary-Fibrosis

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.

Topics: Adenine; Animals; Apoptosis; Bleomycin; Disease Models, Animal; Epithelial Cells; Humans; Idiopathic Pulmonary Fibrosis; Inflammation; Mice; Piperidines; Pulmonary Fibrosis; Pyrazoles; Pyrimidines