[Frontiers in Bioscience 14, 2935-2943, January 1, 2009]
Effects of DC-SIGN expression on renal tubulointerstitial fibrosis in nephritis
Tong Zhou 1
Tong Zhou1, Xiao Li1, Jie Zou1, Minchao Cai1, Guizhi Sun1, Yumei Zhang1, Yapeng Zhao1, Mingjun Zhang2, Yanyun Zhang3, Nan Chen1
1Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui jin Er road, Shanghai 200025, China, 2Laboratory of Animal, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui jin Er road, Shanghai 200025, China, 3Shanghai Institute of Immunology and Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 227 South Chongqing Road, Shanghai 200025, China
TABLE OF CONTENTS
Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) is important for dendritic cell (DC) in migrating, recognizing, capturing, presenting antigens and in initiating T cell responses. In the present study, we investigated the role of DC-SIGN in renal tubulointerstitial inflammation and fibrosis. DC-SIGN was mainly expressed in tubular epithelial cells and DC-SIGN+ DCs were primarily distributed in renal tubulointerstitial areas during the early stage of nephritis, which was correlated with the degree of renal tubular interstitial lesions and fibrosis. In vitro, DC-SIGN expression in cultured human renal tubular epithelial cells was elevated when treated by tumor necrosis factor-alpha, and was inhibited by anti-P-selectin lectin-EGF domain monoclonal antibody (PsL-EGFmAb). In a rat model of chronic renal interstitial fibrosis, there was a significant correlation of DC-SIGN expression with DC-SIGN+ DC distribution and the degree of tubulointerstitial lesion. PsL-EGFmAb reduced DC-SIGN expression and DC-SIGN+ DC accumulation in renal tissues in this rat model. These results suggest that DC-SIGN plays an important role in DC-mediated renal tubular interstitial lesions induced by immuno-inflammatory responses.