title: Translocation of Endogenous Danger Signal HMGB1 From Nucleus to Membrane Microvesicles in Macrophages.
abstract: High mobility group box 1 (HMGB1) is a nuclear protein that can be released from activated or dead cells. Extracellular HMGB1 can serve as a "danger signal" and novel cytokine that mediates sterile inflammation. In addition to its soluble form, extracellular HMGB1 can also be carried by membrane microvesicles. However, the cellular mechanisms responsible for nuclear HMGB1 translocation to the plasma membrane and release onto membrane microvesicles have not been investigated. Tobacco smoking is a major cause of sterile inflammation in many diseases. Smoking also increases blood levels of HMGB1. In this study, we found that exposure of macrophages to tobacco smoke extract (TSE) stimulated HMGB1 expression, redistribution, and release into the extracellular milieu both as a soluble molecule and, surprisingly, as a microvesicle-associated form (TSE-MV). Inhibition of chromosome region maintenance-1 (CRM1), a nuclear exporter, attenuated TSE-induced HMGB1 redistribution from the nucleus to the cytoplasm, and then its release on TSE-MVs. Our study demonstrates a novel mechanism for the translocation of nuclear HMGB1 to the plasma membrane, and then its release in a microvesicle-associated form. J. Cell. Physiol. 231: 2319-2326, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania.|Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China.
authors.forename: Guangping
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.|Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania.
authors.forename: Victoria P
authors.initials: VP
authors.lastname: Werth
authors.affiliation: Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania.|Department of Molecular and Clinical Medicine, Sahlgrenska Academy of the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Kevin Jon
authors.initials: KJ
authors.lastname: Williams
authors.affiliation: Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania.|Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.|Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania.
authors.forename: Ming-Lin
authors.initials: ML
authors.lastname: Liu
mesh_terms: D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D055252:Cell-Derived Microparticles / Q000187:drug effects / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D028884:Karyopherins / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012995:Solubility; D014028:Tobacco Smoke Pollution; D000097606:Exportin 1 Protein
chemical_list: D017077:Culture Media, Conditioned; D024243:HMGB1 Protein; D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear; D014028:Tobacco Smoke Pollution; D000097606:Exportin 1 Protein