HMG-1 rediscovered as a cytokine.
High-mobility group-1 (HMG-1), an abundant, highly conserved cellular protein, is widely known as a nuclear DNA-binding protein that stabilizes nucleosome formation, facilitates gene transcription, and regulates the activity of steroid hormone receptors. We discovered that HMG-1 is a late mediator of delayed endotoxin lethality. When released by activated monocytes, it participates in the development of lethality and it activates downstream cytokine release. This review covers the general features of HMG-1 and its newly appreciated role as a cytokine.
Yang
H
H
Laboratory of Biomedical Science, North Shore University Hospital, Manhasset, New York 11030, USA.
Wang
H
H
Tracey
K J
KJ
D000210:Acute-Phase Reaction / Q000209:etiology; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000097:blood / Q000737:chemistry / Q000235:genetics / Q000502:physiology* / Q000633:toxicity; D016207:Cytokines / Q000502:physiology*; D004331:Drosophila melanogaster / Q000378:metabolism; D019446:Endotoxemia / Q000378:metabolism*; D004731:Endotoxins / Q000494:pharmacology / Q000633:toxicity*; D024243:HMGB1 Protein; D006609:High Mobility Group Proteins / Q000097:blood / Q000737:chemistry / Q000235:genetics / Q000502:physiology* / Q000633:toxicity; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D019476:Insect Proteins / Q000737:chemistry / Q000502:physiology; D007375:Interleukin-1 / Q000494:pharmacology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects; D008954:Models, Biological; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D005810:Multigene Family; D010903:Pituitary Gland, Anterior / Q000166:cytology; D011499:Protein Processing, Post-Translational; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D012772:Shock, Septic / Q000209:etiology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014714:Vertebrates / Q000378:metabolism
D002352:Carrier Proteins; D016207:Cytokines; D004731:Endotoxins; D024243:HMGB1 Protein; D006609:High Mobility Group Proteins; D018836:Inflammation Mediators; D019476:Insect Proteins; D007375:Interleukin-1; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha