title: Calcitriol inhibits bleomycin-induced early pulmonary inflammatory response and epithelial-mesenchymal transition in mice.
abstract: 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 (3.0mg/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.
authors.affiliation: Second Affiliated Hospital, Anhui Medical University, Hefei 230022, China.
authors.forename: Zhu-Xia
authors.initials: ZX
authors.lastname: Tan
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei 230032, China; Department of Histology and Embryology, Anhui Medical University, Hefei 230032, China.
authors.forename: Yuan-Hua
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Second Affiliated Hospital, Anhui Medical University, Hefei 230022, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Xu
authors.affiliation: Second Affiliated Hospital, Anhui Medical University, Hefei 230022, China.
authors.forename: Hou-Ying
authors.initials: HY
authors.lastname: Qin
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei 230032, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Second Affiliated Hospital, Anhui Medical University, Hefei 230022, China. Electronic address: zhaohuichenxi@126.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei 230032, China. Electronic address: xudex@126.com.
authors.forename: De-Xiang
authors.initials: DX
authors.lastname: Xu
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001761:Bleomycin / Q000633:toxicity*; D002117:Calcitriol / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005819:Genetic Markers; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D000893:Anti-Inflammatory Agents; D005819:Genetic Markers; D051996:Transcription Factor RelA; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D002117:Calcitriol
keywords: Bleomycin; Calcitriol; Epithelial–mesenchymal transition; Inflammation; Lung; Mice; Nuclear factor kappa B p65