title: Calcitriol inhibits tumor necrosis factor alpha and macrophage inflammatory protein-2 during lipopolysaccharide-induced acute lung injury in mice.
abstract: Acute lung injury is a common complication of sepsis in intensive care unit patients with an extremely high mortality. The present study investigated the effects of calcitriol, the active form of vitamin D, on tumor necrosis factor alpha (TNF-α) and macrophage inflammatory protein-2 (MIP-2) in sepsis-induced acute lung injury. Mice were intraperitoneally (i.p.) injected with lipopolysaccharide (LPS, 1.0mg/kg) to establish the animal model of sepsis-induced acute lung injury. Some mice were i.p. injected with calcitriol (1.0μg/kg) before LPS injection. An obvious infiltration of inflammatory cells in the lungs was observed beginning at 1h after LPS injection. Correspondingly, TNF-α and MIP-2 in sera and lung homogenates were markedly elevated in LPS-treated mice. Interestingly, calcitriol obviously alleviated LPS-induced infiltration of inflammatory cells in the lungs. Moreover, calcitriol markedly attenuated LPS-induced elevation of TNF-α and MIP-2 in sera and lung homogenates. Further analysis showed that calcitriol repressed LPS-induced p38 mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) phosphorylation. In addition, calcitriol blocked LPS-induced nuclear translocation of nuclear factor kappa B (NF-κB) p65 and p50 subunit in the lungs. Taken together, these results suggest that calcitriol inhibits inflammatory cytokines production in LPS-induced acute lung injury.
authors.affiliation: The Second Affiliated Hospital, Anhui Medical University, Hefei, China.
authors.forename: Zhu-Xia
authors.initials: ZX
authors.lastname: Tan
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei, China; Department of Histology and Embryology, Anhui Medical University, Hefei, China.
authors.forename: Yuan-Hua
authors.initials: YH
authors.lastname: Chen
authors.affiliation: The Second Affiliated Hospital, Anhui Medical University, Hefei, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Xu
authors.affiliation: The Second Affiliated Hospital, Anhui Medical University, Hefei, China.
authors.forename: Hou-Ying
authors.initials: HY
authors.lastname: Qin
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei, China. Electronic address: xudex@126.com.
authors.forename: De-Xiang
authors.initials: DX
authors.lastname: Xu
authors.affiliation: The Second Affiliated Hospital, Anhui Medical University, Hefei, China. Electronic address: zhaohuichenxi@126.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology* / Q000627:therapeutic use*; D054426:Chemokine CXCL2 / Q000097:blood / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D015151:Immunoblotting; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism*
chemical_list: D054426:Chemokine CXCL2; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D002117:Calcitriol
keywords: Acute lung injury; Calcitriol; Inflammatory cytokines; Lipopolysaccharide; Nuclear factor kappa B