title: Members of the receptor for advanced glycation end products axis as potential therapeutic targets in patients with lupus nephritis.
abstract: The relationship of inflammation and the expression of full-length receptor for advanced glycation end products (flRAGE) on monocytes, plasma levels of RAGE ligand high mobility group box protein 1 (HMGB1), soluble RAGE (sRAGE) and endogenous secretory RAGE (esRAGE) was assessed to elucidate the effect of HMGB1/DNA/RAGE-mediated innate inflammatory responses in patients with lupus nephritis. Cell surface expression of flRAGE was elevated on the monocytes of lupus patients, correlated with plasma HMGB1 levels. Plasma sRAGE level negatively correlated with systemic lupus erythematosus (SLE) disease activity index. Plasma esRAGE level was significantly lower in SLE patients with flare while esRAGE/sRAGE ratio negatively correlated with complement C3 level. HMGB1 alone could moderately induce ex vivo IL-6 production from monocytes, resulting in activation of intracellular p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase and nuclear factor (NF)-κB. Moreover, toll-like receptor-9 ligand together with HMGB1 exhibited a synergistic effect on IL-6 and IL-12p70 secretions and the phosphorylation of p38 MAPK and NF-κB. Therefore, over-expression of flRAGE in lupus may lead to the amplification of RAGE ligands-mediated inflammatory responses through the activation of p38 MAPK and NF-κB. Plasma sRAGE may serve as a potential biomarker for disease activity and a future therapeutic target in SLE.
authors.affiliation: Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China Department of Rheumatology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University (GZMU), Guangdong, China.
authors.forename: S L
authors.initials: SL
authors.lastname: Yu
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
authors.forename: C K
authors.initials: CK
authors.lastname: Wong
authors.affiliation: Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors.forename: C C
authors.initials: CC
authors.lastname: Szeto
authors.affiliation: Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors.forename: E K
authors.initials: EK
authors.lastname: Li
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China. lstam@cuhk.edu.hk.
authors.forename: L S
authors.initials: LS
authors.lastname: Tam
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005921:Glomerulonephritis / Q000097:blood / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000097:blood; D024243:HMGB1 Protein / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000097:blood; D008181:Lupus Nephritis / Q000097:blood*; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000097:blood*; D048051:p38 Mitogen-Activated Protein Kinases / Q000097:blood
chemical_list: C000593871:AGER protein, human; D015415:Biomarkers; D016207:Cytokines; D017127:Glycation End Products, Advanced; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D015850:Interleukin-6; D000067759:Receptor for Advanced Glycation End Products; D048051:p38 Mitogen-Activated Protein Kinases
keywords: HMGB1; RAGE; inflammatory cytokines; lupus nephritis; mitogen-activated protein kinase