OM85 ameliorates bleomycin-induced pulmonary fibrosis in mice by inhibiting Notch expression and modulating the Th1/Th2 balance

Abstract

Abstract Th1/Th2 balances may play a vital role in the processes of inflammation and fibrosis. OM-85 BV encouraged preferential development of the Th1-type immunity characterized by amplified IFN-γ and decreased IL-4 production. The objective of this study was to evaluate the inhibitory effect of OM85 on bleomycin (BLM)-induced pulmonary fibrosis in C57 and its possible mechanisms. In vitro experiments, OM85 inhibited protein expression of Notch1 and Hes1 induced by TGF-β1 and influence proliferation of fibroblast cell. OM85 also reduced the α-SMA expression induced by TGF-β1 in fibroblast. In vivo experiments, pulmonary fibrosis model was established by three-dose intratracheal instillation of BLM (1mg/kg). While control C57 received saline, C57 of the treated group simultaneously were then exposed to an aerosol containing 10.5 mg of OM85 dissolved in 10 mL of sterile PBS solution at day42,44,46,49,51,53. BLM induced pulmonary fibrosis, increased lung hydroxyproline levels, total cell counts, macrophages, neutrophils and Lymphocytes counts and expression of Notch1 and Hes1 in lung tissue. In addition, Th1 response is suppressed as shown by diminished IFN-γ in bronchoalveolar lavage fluid (BALF), and enhancement of Th2 response is marked by increased IL-4 in BALF. OM85 administration significantly attenuated these effects. The findings reveal the therapeutic potential of OM85 for BLM-induced pulmonary fibrosis in female C57, which were at least partly due to inhibition notch1 and Hes1 expression and regulation of Th1/Th2 balance.