title: High-mobility group box 1 inhibition alleviates lupus-like disease in BXSB mice.
abstract: High-mobility group box 1 protein (HMGB1), a ubiquitous nuclear DNA-binding protein, functions as a potent proinflammatory factor. In this study, we evaluated the effects of HMGB1 inhibition on murine lupus using the lupus-prone model. We treated male BXSB mice with neutralizing anti-HMGB1 monoclonal antibody (HMGB1 mAb) from age 16 weeks to 26 weeks. The control group received the same amount of control IgG. Lupus-prone male BXSB mice treated with HMGB1mAb showed attenuated proteinuria, glomerulonephritis, circulating anti-dsDNA and immune complex deposition. Levels of serum IL-1β, IL-6, IL-17 and IL-18 were also significantly decreased by administration of HMGB1mAb in lupus-prone BXSB mice. HMGB1mAb treatment also decreased the caspase-1 activity in the kidneys of BXSB mice and reduced the mouse mortality. Our study supports that HMGB1 inhibition alleviates lupus-like disease in BXSB mice and might be a potential treatment option for human SLE.
authors.affiliation: Department of Rheumatology, Jinan Central Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Jia
authors.forename: P
authors.initials: P
authors.lastname: Yao
authors.forename: Q
authors.initials: Q
authors.lastname: Yang
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage*; D020170:Caspase 1 / Q000378:metabolism; D003404:Creatinine / Q000652:urine; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D058990:Molecular Targeted Therapy; D013154:Spleen / Q000187:drug effects* / Q000473:pathology
chemical_list: D000418:Albumins; D019138:Antibodies, Blocking; D016207:Cytokines; D024243:HMGB1 Protein; D004247:DNA; D003404:Creatinine; D020170:Caspase 1