| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2598602 | Toxicology Letters | 2016 | 11 Pages |
•Calcitriol attenuates BLM-induced inflammatory cytokines in the lungs.•Calcitriol inhibits BLM-activated NF-κB signaling in the lungs.•Calcitriol inhibits BLM-activated PI3K/Akt and p38 MAPK in the lungs.•Calcitriol inhibits BLM-induced EMT in the lungs.•Calcitriol inhibits BLM-activated TGF-β-Smad signaling in the lungs.
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. Mice were intratracheally injected with BLM (3.0 mg/kg). In three calcitriol + BLM groups, mice were intraperitoneal (i.p.) injected with different doses of calcitriol (0.2, 1.0 or 5.0 μg/kg) daily, beginning at 48 h before BLM injection. Twenty-four hours, seven and fourteen days after BLM injection, pulmonary inflammation and EMT were evaluated. 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, BLM-induced nuclear translocation of nuclear factor kappa B (NF-κB) 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 α-smooth muscle actin (α-SMA), a marker for EMT in the lungs, was significantly attenuated by calcitriol. BLM-induced transforming growth factor-beta 1 (TGF-β1) up-regulation and Smad phosphorylation were attenuated by calcitriol. In conclusion, calcitriol inhibits BLM-induced early pulmonary inflammation and subsequent EMT.
