DC-SIGN reacts with TLR-4 and regulates inflammatory cytokine expression via NF-κB activation in renal tubular epithelial cells during acute renal injury
Open Access
- 12 September 2017
- journal article
- research article
- Published by Oxford University Press (OUP) in Clinical and Experimental Immunology
- Vol. 191 (1), 107-115
- https://doi.org/10.1111/cei.13048
Abstract
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.Funding Information
- National Natural Science Foundation of China (81200204, 81470547, 81770384, 81170363, 81270801, 81470941)
- Natural Science Foundation of Shanghai (15ZR1426100)
This publication has 32 references indexed in Scilit:
- Sepsis-Associated AKI: Epithelial Cell DysfunctionSeminars in Nephrology, 2015
- Acute Kidney Injury in Patients with Sepsis and Septic Shock: Risk Factors and Clinical OutcomesYonsei Medical Journal, 2013
- Histones from Dying Renal Cells Aggravate Kidney Injury via TLR2 and TLR4Journal of the American Society of Nephrology, 2012
- DC-SIGN modulates DC maturation and function in rat renal tubulointerstitial lesionsFrontiers in Bioscience-Landmark, 2012
- Role of Proximal Tubules in the Pathogenesis of Kidney DiseasePublished by S. Karger AG ,2011
- Potential Interventions in Sepsis-Related Acute Kidney InjuryClinical Journal of the American Society of Nephrology, 2008
- TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-βNature Immunology, 2008
- Association of SIGNR1 with TLR4–MD-2 enhances signal transduction by recognition of LPS in gram-negative bacteriaInternational Immunology, 2005
- Dendritic cells as a tool to induce anergic and regulatory T cellsTrends in Immunology, 2001
- Murine epidermal Langerhans cells and splenic dendritic cells present tumor-associated antigens to primed T cellsEuropean Journal of Immunology, 1994