Journal
TOXICOLOGY LETTERS
Volume 240, Issue 1, Pages 161-171Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2015.10.022
Keywords
Calcitriol; Bleomycin; Inflammation; Nuclear factor kappa B p65; Epithelial-mesenchymal transition; Lung; Mice
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Funding
- National Natural Science Foundation of China [30671786, 31000664, 81471467]
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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 mu g/kg). In three calcitriol + BLM groups, mice were intraperitoneal (i.p.) injected with different doses of calcitriol (0.2, 1.0 or 5.0 mu g/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-kappa 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 alpha-smooth muscle actin (alpha-SMA), a marker for EMT in the lungs, was significantly attenuated by calcitriol. BLM-induced transforming growth factor-beta 1 (TGF-beta 1) up-regulation and Smad phosphorylation were attenuated by calcitriol. In conclusion, calcitriol inhibits BLM-induced early pulmonary inflammation and subsequent EMT. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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