title: Vitamin D3 pretreatment regulates renal inflammatory responses during lipopolysaccharide-induced acute kidney injury.
abstract: Vitamin D receptor (VDR) is highly expressed in human and mouse kidneys. Nevertheless, its functions remain obscure. This study investigated the effects of vitamin D3 (VitD3) pretreatment on renal inflammation during lipopolysaccharide (LPS)-induced acute kidney injury. Mice were intraperitoneally injected with LPS. In VitD3 + LPS group, mice were pretreated with VitD3 (25 μg/kg) at 48, 24 and 1 h before LPS injection. As expected, an obvious reduction of renal function and pathological damage was observed in LPS-treated mice. VitD3 pretreatment significantly alleviated LPS-induced reduction of renal function and pathological damage. Moreover, VitD3 pretreatment attenuated LPS-induced renal inflammatory cytokines, chemokines and adhesion molecules. In addition, pretreatment with 1,25(OH)2D3, the active form of VitD3, alleviated LPS-induced up-regulation of inflammatory cytokines and chemokines in human HK-2 cells, a renal tubular epithelial cell line, in a VDR-dependent manner. Further analysis showed that VitD3, which activated renal VDR, specifically repressed LPS-induced nuclear translocation of nuclear factor kappa B (NF-κB) p65 subunit in the renal tubules. LPS, which activated renal NF-κB, reciprocally suppressed renal VDR and its target gene. Moreover, VitD3 reinforced the physical interaction between renal VDR and NF-κB p65 subunit. These results provide a mechanistic explanation for VitD3-mediated anti-inflammatory activity during LPS-induced acute kidney injury.
authors.affiliation: The Second Affiliated Hospital, Anhui Medical University, Hefei, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Xu
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: Zhu-Xia
authors.initials: ZX
authors.lastname: Tan
authors.affiliation: The Second Affiliated Hospital, Anhui Medical University, Hefei, China.
authors.forename: Dong-Dong
authors.initials: DD
authors.lastname: Xie
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.
authors.forename: Zhi-Hui
authors.initials: ZH
authors.lastname: Zhang
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: The Second Affiliated Hospital, Anhui Medical University, Hefei, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: The Second Affiliated Hospital, Anhui Medical University, Hefei, China.
authors.forename: De-Xin
authors.initials: DX
authors.lastname: Yu
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei, China.
authors.forename: De-Xiang
authors.initials: DX
authors.lastname: Xu
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D000818:Animals; D002460:Cell Line; D018925:Chemokines / Q000378:metabolism; D002762:Cholecalciferol / Q000494:pharmacology / Q000627:therapeutic use*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000188:drug therapy*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000378:metabolism; D014162:Transfection; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018925:Chemokines; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; D018167:Receptors, Calcitriol; D051996:Transcription Factor RelA; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D002762:Cholecalciferol; D051546:Cyclooxygenase 2; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases