bay-11-7082 and Idiopathic-Pulmonary-Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible lung disease of unknown cause. It has been reported that both lung resident mesenchymal stem cells (LR-MSCs) and tumor necrosis factor-α (TNF-α) play important roles in the development of pulmonary fibrosis. However, the underlying connections between LR-MSCs and TNF-α in the pathogenesis of pulmonary fibrosis are still elusive. In this study, we found that the pro-inflammatory cytokine TNF-α and the transcription factor nuclear factor kappa B (NF-κB) p65 subunit were both upregulated in bleomycin-induced fibrotic lung tissue. In addition, we discovered that TNF-α promotes myofibroblast differentiation of LR-MSCs through activating NF-κB signaling. Interestingly, we also found that TNF-α promotes the expression of β-catenin. Moreover, we demonstrated that suppression of the NF-κB signaling could attenuate myofibroblast differentiation of LR-MSCs and bleomycin-induced pulmonary fibrosis which were accompanied with decreased expression of β-catenin. Our data implicates that inhibition of the NF-κB signaling pathway may provide a therapeutic strategy for pulmonary fibrosis, a disease that warrants more effective treatment approaches.

Topics: Animals; beta Catenin; Bleomycin; Cell Differentiation; Cells, Cultured; Disease Models, Animal; Dose-Response Relationship, Drug; Idiopathic Pulmonary Fibrosis; Lung; Male; Mesenchymal Stem Cells; Mice, Inbred C57BL; Myofibroblasts; Nitriles; Sulfones; Time Factors; Transcription Factor RelA; Tumor Necrosis Factor-alpha; Up-Regulation; Wnt Signaling Pathway