title: HMGB1 Promotes Systemic Lupus Erythematosus by Enhancing Macrophage Inflammatory Response.
abstract: Background/Purpose. HMGB1, which may act as a proinflammatory mediator, has been proposed to contribute to the pathogenesis of multiple chronic inflammatory and autoimmune diseases including systemic lupus erythematosus (SLE); however, the precise mechanism of HMGB1 in the pathogenic process of SLE remains obscure. Method. The expression of HMGB1 was measured by ELISA and western blot. The ELISA was also applied to detect proinflammatory cytokines levels. Furthermore, nephritic pathology was evaluated by H&E staining of renal tissues. Results. In this study, we found that HMGB1 levels were significantly increased and correlated with SLE disease activity in both clinical patients and murine model. Furthermore, gain- and loss-of-function analysis showed that HMGB1 exacerbated the severity of SLE. Of note, the HMGB1 levels were found to be associated with the levels of proinflammatory cytokines such as TNF-α and IL-6 in SLE patients. Further study demonstrated that increased HMGB1 expression deteriorated the severity of SLE via enhancing macrophage inflammatory response. Moreover, we found that receptor of advanced glycation end products played a critical role in HMGB1-mediated macrophage inflammatory response. Conclusion. These findings suggested that HMGB1 might be a risk factor for SLE, and manipulation of HMGB1 signaling might provide a therapeutic strategy for SLE.
authors.affiliation: Institute for Immunobiology and Department of Immunology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Mudan
authors.initials: M
authors.lastname: Lu
authors.affiliation: Institute for Immunobiology and Department of Immunology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Yu
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Wei
authors.identifier: 0000-0003-2652-8244
authors.initials: W
authors.lastname: Xu
authors.affiliation: Institute for Immunobiology and Department of Immunology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Gao
authors.affiliation: Institute for Immunobiology and Department of Immunology, Shanghai Medical College, Fudan University, Shanghai 200032, China ; Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Sidong
authors.initials: S
authors.lastname: Xiong
mesh_terms: D000328:Adult; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood / Q000276:immunology; D016022:Case-Control Studies; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D024243:HMGB1 Protein / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism; D012720:Severity of Illness Index; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D055815:Young Adult
chemical_list: D000974:Antibodies, Antinuclear; D016207:Cytokines; D024243:HMGB1 Protein; D018836:Inflammation Mediators; D000067759:Receptor for Advanced Glycation End Products; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4