DC-SIGN reacts with TLR-4 and regulates inflammatory cytokine expression via NF-κB activation in renal tubular epithelial cells during acute renal injury. (5th October 2017)

• Record Type: Journal Article
• Authors: Feng, D; Wang, Y; Liu, Y; Wu, L; Li, X; Chen, Y; Chen, Y; Chen, Y; Xu, C; Yang, K; Zhou, T
• Is Part Of: Clinical and experimental immunology. Volume 191:Number 1(2018:Jan.)
• Page Start: 107
• Page End: 115
• Publication Date: 2017-10-05
• Subjects: acute kidney injury -- DC-SIGN -- NF-κB -- renal tubular epithelial cells -- TLR-4; Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.13048
• Languages: English
• ISSNs: 0009-9104

Abstract

Summary: In the pathological process of acute kidney injury (AKI), innate immune receptors are essential in inflammatory response modulation; however, the precise molecular mechanisms are still unclear. Our study sought to demonstrate the inflammatory response mechanisms in renal tubular epithelial cells via Toll-like receptor-4 (TLR-4) and dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin 1 (DC-SIGN) signalling. We found that DC-SIGN exhibited strong expression in renal tubular epithelial cells of human acute renal injury tissues. DC-SIGN protein expression was increased significantly when renal tubular epithelial cells were exposed to lipopolysaccharide (LPS) for a short period. Furthermore, DC-SIGN was involved in the activation of p65 by TLR-4, which excluded p38 and c-Jun N-terminal kinases (JNK). Interleukin (IL)-6 and tumour necrosis factor (TNF)-α expression was decreased after DC-SIGN knock-down, and LPS induced endogenous interactions and plasma membrane co-expression between TLR-4 and DC-SIGN. These results show that DC-SIGN and TLR-4 interactions regulate inflammatory responses in renal tubular epithelial cells and participate in AKI pathogenesis. Graphical Abstract: