title: Release and activity of histone in diseases.
abstract: Histones and their post-translational modifications have key roles in chromatin remodeling and gene transcription. Besides intranuclear functions, histones act as damage-associated molecular pattern molecules when they are released into the extracellular space. Administration of exogenous histones to animals leads to systemic inflammatory and toxic responses through activating Toll-like receptors and inflammasome pathways. Anti-histone treatment (e.g., neutralizing antibodies, activated protein C, recombinant thrombomodulin, and heparin) protect mice against lethal endotoxemia, sepsis, ischemia/reperfusion injury, trauma, pancreatitis, peritonitis, stroke, coagulation, and thrombosis. In addition, elevated serum histone and nucleosome levels have been implicated in multiple pathophysiological processes and progression of diseases including autoimmune diseases, inflammatory diseases, and cancer. Therefore, extracellular histones could serve as biomarkers and novel therapeutic targets in human diseases.
authors.affiliation: 1] Department of Infectious Diseases and State Key Lab of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan, China [2] Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kang
authors.affiliation: Department of Infectious Diseases and State Key Lab of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: X-G
authors.initials: XG
authors.lastname: Fan
authors.affiliation: Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Tang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000378:metabolism / Q000473:pathology; D044127:Epigenesis, Genetic; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009707:Nucleosomes / Q000378:metabolism; D010195:Pancreatitis / Q000378:metabolism / Q000473:pathology; D010538:Peritonitis / Q000378:metabolism / Q000473:pathology; D011499:Protein Processing, Post-Translational; D018805:Sepsis / Q000378:metabolism / Q000473:pathology; D013927:Thrombosis / Q000378:metabolism / Q000473:pathology
chemical_list: D006657:Histones; D009707:Nucleosomes