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2017 ; 12
(2
): e0172536
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Protective effect of 1?,25-dihydroxyvitamin D3 on effector CD4+ T cell induced
injury in human renal proximal tubular epithelial cells
#MMPMID28245293
Chung BH
; Kim BM
; Doh KC
; Cho ML
; Kim KW
; Yang CW
PLoS One
2017[]; 12
(2
): e0172536
PMID28245293
show ga
BACKGROUND: The aim of this study was to investigate the protective effect of
1?,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-?, IL-17, and
TGF-?) 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. CONCLUSION: 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. TRIAL REGISTRATION: 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).