title: HMGB1 as a mediator of necrosis-induced inflammation and a therapeutic target in arthritis.
abstract: For the second time in recent history, studies directed at the pathogenesis of infectious disease have led to the identification of an endogenous mediator of arthritis. HMGB1, a 30-kD nuclear and cytoplasmic protein widely studied as a DNA-binding protein, is a newly described cytokine and a necessary and sufficient mediator of lethal sepsis. HMGB1 is passively released during cell necrosis, but not apoptosis; it activates an inflammatory response to necrosis,but not apoptosis. Furthermore, HMGB1 can also be actively secreted by stimulated macrophages or monocytes in a process that requires acetylation of the molecule, enabling a translocation from the nucleus to secretory lysosomes. Recent evidence indicates that HMGB1 is a mediator of arthritis because of the following: (1) it is produced at the site of joint inflammation, (2) it causes the development of arthritis when applied to normal joints, and (3) therapies that inhibit HMGB1 prevent the progression of collagen-induced arthritis in rodents. Anti-HMGB1 may be studied in future clinical trials of diseases of excessive production of HMGB1, such as severe sepsis and arthritis.
authors.affiliation: Department of Woman and Child Health, Karolinska Institutet, Astrid Lindgren Children's Hospital, Stockholm, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Andersson
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Tracey
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*
chemical_list: D024243:HMGB1 Protein; D018836:Inflammation Mediators