DC-SIGN reacts with TLR4 and regulates inflammatory cytokine expression via NF-κB activation in renal tubular epithelial cells during acute renal injury

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 (TLR4) and dendritic cell-specific ICAM-3-grabbing non-integrin 1 (DC-SIGN) signaling. We found that DC-SIGN exhibited strong expression in renal tubular epithelial cells of human acute renal injury tissues. DC-SIGN protein expression was significantly increased 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 TLR4, which excluded p38 and JNK. Interleukin 6 (IL-6) and tumor necrosis factor-α (TNFα) expression were decreased after DC-SIGN knockdown. Furthermore, LPS induced endogenous interactions and plasma membrane co-expression between TLR4 and DC-SIGN. These results showed that DC-SIGN and TLR4 interactions regulate inflammatory responses in renal tubular epithelial cells and participate in AKI pathogenesis. This article is protected by copyright. All rights reserved.