Calcitriol Inhibits Bleomycin-induced Early Pulmonary Inflammatory Response And Epithelial–mesenchymal Transition In Mice

Objective: Early pulmonary inflammation and epithelial–mesenchymal transition(EMT)play important roles during lung fibrosis.Increasing evidence demonstrates that calcitriol,the active form of vitamin D3,has anti-inflammatory activities.The aim of this study was to investigate the effects of calcitriol on bleomycin(BLM)-induced early pulmonary inflammation and subsequent EMT.Method: Adult male C57BL/6J mice(8 week-old,24–26 g)were purchased ?In BLM group,mice were intratracheally injected with BLM(3.0 mg/kg)in 50 ul phosphate buffered saline.In three calcitriol + BLM groups,mice were intraperitoneal(i.p.)injected with different doses of calcitriol(0.2,1.0 or 5.0 mg/kg)daily,beginning at 48 h,at 24 h,at 1 h before BLM injection.Twentyfour hours,seven and fourteen days after BLM injection,pulmonary inflammation and EMT were evaluated.Result: As expected,BLM-induced infiltration of inflammatory cells in the lungs was attenuated by calcitriol.BLM-induced pulmonary inflammatory cytokines were repressed by calcitriol.Moreover,BLMinduced nuclear translocation of nuclear factor kappa B(NF-k B)p65 was blocked by calcitriol.In addition,BLM-induced phosphorylation of pulmonary p38 MAPK and protein kinase B(Akt)was inhibited by calcitriol.Further analysis showed that BLM-induced a-smooth muscle actin(a-SMA),a marker for EMT in the lungs,was significantly attenuated by calcitriol.BLM-induced transforming growth factor-beta 1(TGF-b1)up-regulation and Smad phosphorylation were attenuated by calcitriol.Conclusion: In conclusion,calcitriol inhibits BLM-induced early pulmonary inflammation and subsequent EMT.