title: Protective effect of 1α,25-dihydroxyvitamin D3 on effector CD4+ T cell induced injury in human renal proximal tubular epithelial cells.
abstract: BACKGROUND
  The aim of this study was to investigate the protective effect of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] on effector CD4+ T cells or on inflammatory cytokine-induced injury in human renal proximal tubular epithelial cells (HRPTEpiC).
  
  
  METHODS
  First, we investigated the effect of 1,25(OH)2D3 on CD4+ T cell proliferation. Second, we examined the effect of 1,25(OH)2D3 on inflammatory cytokine secretion or fibrosis in HRPTEpiC induced by inflammatory cytokines or activated CD4+ T cells using ELISA and real-time PCR. Lastly, we compared urine inflammatory-cytokine (IL-6, IL-8) or KIM-1 levels in kidney transplant recipients low serum 25-hydroxyvitamin D (25(OH)D) group (< 20 ng/mL) (n = 40) and normal 25(OH)D group (n = 50).
  
  
  RESULTS
  Pre-incubation with 1,25(OH)2D3 significantly reduced the percentages of Th1 and Th17 cells compared to that of Th0 condition (P < 0.05 for each). In contrast, 1,25(OH)2D3 increased the proportion of Th2 and Treg cells in a dose-dependent manner (P < 0.05 for each). Treatment of HRPTEpiC with inflammatory cytokines (TNF-α, IL-17, and TGF-β) or effector CD4+ T cells resulted in increased production of IL-6, IL-8, or KIM-1 from HRPTEpiC in a dose-dependent manner. However, treatment with 1,25(OH)2D3 significantly reduced the level of these cytokines (P < 0.05 for all). Western blot analysis demonstrated that the mTOR/STAT3/ERK pathway was downregulated by 1,25(OH)2D3 in HRPTEpiC. Furthermore, the concentrations of urine IL-6/creatinine (P < 0.05) and Kim-1/creatinine (P < 0.05) were higher in the low 25(OH)D group than in the normal 25(OH)D group in kidney transplant recipients.
  
  
  CONCLUSIONS
  The results of this study suggests that vitamin D may have a significant role in the regulation of inflammation in allograft tissue in kidney transplant recipients.
  
  
  BACKGROUND
  All participants provided written informed consent in accordance with the Declaration of Helsinki. This study was approved by the Institutional Review Board of Seoul St. Mary's Hospital (KC13TNMI0701).
authors.affiliation: Convergent Research Consortium for Immunologic Disease, The Catholic University of Korea Seoul, Korea.|Transplant Research Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.|Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Byung Ha
authors.initials: BH
authors.lastname: Chung
authors.affiliation: Convergent Research Consortium for Immunologic Disease, The Catholic University of Korea Seoul, Korea.
authors.forename: Bo-Mi
authors.initials: BM
authors.lastname: Kim
authors.affiliation: Convergent Research Consortium for Immunologic Disease, The Catholic University of Korea Seoul, Korea.|Transplant Research Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Kyoung Chan
authors.initials: KC
authors.lastname: Doh
authors.affiliation: Convergent Research Consortium for Immunologic Disease, The Catholic University of Korea Seoul, Korea.
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
authors.affiliation: Convergent Research Consortium for Immunologic Disease, The Catholic University of Korea Seoul, Korea.|Transplant Research Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Kyoung Woon
authors.initials: KW
authors.lastname: Kim
authors.affiliation: Convergent Research Consortium for Immunologic Disease, The Catholic University of Korea Seoul, Korea.|Transplant Research Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.|Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Chul Woo
authors.identifier: http://orcid.org/0000-0001-9796-636X
authors.initials: CW
authors.lastname: Yang
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D005353:Fibronectins / Q000235:genetics; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000235:genetics; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D016207:Cytokines; C067625:FN1 protein, human; D005353:Fibronectins; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D020381:Interleukin-17; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C118756:dihydroxy-vitamin D3; D014807:Vitamin D