期刊
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
卷 19, 期 9, 页码 1741-1752出版社
AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2007060666
关键词
-
资金
- National Institutes of Health [DK061408, DK064005, DK071040]
- Abbott Laboratories
- American Heart Association Great Rivers Affiliate
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK064005, R01DK071040, R01DK061408] Funding Source: NIH RePORTER
Inflammation is a pathologic feature of a variety of chronic kidney diseases. Several lines of evidence suggest a potential anti-inflammatory role for vitamin D in chronic kidney disease, but the underlying mechanism remains unknown. Here, the effect of the synthetic vitamin D analogue paricalcitol on renal inflammation was investigated in a mouse model of obstructive nephropathy. Paricalcitol reduced infiltration of T cells and macrophages in the obstructed kidney. This inhibition of inflammatory cell infiltration was accompanied by a decreased expression of RANTES and TNF-alpha. Induction of RANTES was localized primarily to the tubular epithelium, underscoring a role for tubular cells in renal inflammation. In a human proximal tubular cell line (HKC-8), paricalcitol inhibited RANTES mRNA and protein expression and abolished the ability of tubular cells to recruit lymphocytes and monocytes after TNF-alpha stimulation. Although RANTES induction depended on NF-kappa B signaling, paricalcitol affected neither TNF-alpha-mediated I kappa B alpha phosphorylation and degradation nor p65 NF-kappa B activation and nuclear translocation. Instead, chromatin immunoprecipitation assay showed that paricalcitol abolished the binding of p65 to its cognate cis-acting element in the RANTES promoter. The vitamin D receptor (VDR) and p65 formed a complex in tubular cells after paricalcitol treatment, which inhibited the ability of p65 to trans-activate gene transcription. In vivo, paricalcitol did not block NF-kappa B nuclear translocation after obstructive injury but did increase the expression and nuclear distribution of VDR. These results suggest that paricalcitol inhibits renal inflammatory infiltration and RANTES expression by promoting VDR-mediated sequestration of NF-kappa B signaling.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据