title: The role of high mobility group box chromosomal protein 1 in rheumatoid arthritis.
abstract: High mobility group box chromosomal protein 1 (HMGB1) is a ubiquitous highly conserved single polypeptide in all mammal eukaryotic cells. HMGB1 exists mainly within the nucleus and acts as a DNA chaperone. When passively released from necrotic cells or actively secreted into the extracellular milieu in response to appropriate signal stimulation, HMGB1 binds to related cell signal transduction receptors, such as RAGE, TLR2, TLR4 and TLR9, and becomes a proinflammatory cytokine that participates in the development and progression of many diseases, such as arthritis, acute lung injury, graft rejection immune response, ischaemia reperfusion injury and autoimmune liver damage. Only a small amount of HMGB1 release occurs during apoptosis, which undergoes oxidative modification on Cys106 and delivers tolerogenic signals to suppress immune activity. This review focuses on the important role of HMGB1 in the pathogenesis of RA, mainly manifested as the aberrant expression of HMGB1 in the serum, SF and synovial tissues; overexpression of signal transduction receptors; abnormal regulation of osteoclastogenesis and bone remodelling leading to the destruction of cartilage and bones. Intervention with HMGB1 may ameliorate the pathogenic conditions and attenuate disease progression of RA. Therefore administration of an HMGB1 inhibitor may represent a promising clinical approach for the treatment of RA.
authors.affiliation: Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095th Jiefang Avenue, Wuhan, Hubei 430030, China. dongll@tjh.tjmu.edu.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.forename: Rongfen
authors.initials: R
authors.lastname: Gao
authors.forename: Yuying
authors.initials: Y
authors.lastname: Su
authors.forename: Hisanori
authors.initials: H
authors.lastname: Umehara
authors.forename: Lingli
authors.initials: L
authors.lastname: Dong
authors.forename: Feili
authors.initials: F
authors.lastname: Gong
mesh_terms: D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism
chemical_list: D018501:Antirheumatic Agents; D024243:HMGB1 Protein; D018836:Inflammation Mediators
keywords: HMGB1; HMGB1 inhibitors; rheumatoid arthritis; signal transduction