Journal ArticleDOI
HMG-1 as a Late Mediator of Endotoxin Lethality in Mice
Haichao Wang,Ona Bloom,Minghuang Zhang,Jaideep M. Vishnubhakat,Michael Ombrellino,Jiantu Che,Asia Frazier,Huan Yang,Svetlana Ivanova,Lyudmila V. Borovikova,Kirk R. Manogue,Eugen Faist,Edward Abraham,Jan Andersson,Ulf Andersson,Patricia E. Molina,Naji N. Abumrad,Andrew E. Sama,Kevin J. Tracey +18 more
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TLDR
High mobility group-1 (HMG-1) protein was found to be released by cultured macrophages more than 8 hours after stimulation with endotoxin, TNF, or IL-1, and showed increased serum levels after endotoxin exposure, suggesting that this protein warrants investigation as a therapeutic target.Abstract:
Endotoxin, a constituent of Gram-negative bacteria, stimulates macrophages to release large quantities of tumor necrosis factor (TNF) and interleukin-1 (IL-1), which can precipitate tissue injury and lethal shock (endotoxemia). Antagonists of TNF and IL-1 have shown limited efficacy in clinical trials, possibly because these cytokines are early mediators in pathogenesis. Here a potential late mediator of lethality is identified and characterized in a mouse model. High mobility group-1 (HMG-1) protein was found to be released by cultured macrophages more than 8 hours after stimulation with endotoxin, TNF, or IL-1. Mice showed increased serum levels of HMG-1 from 8 to 32 hours after endotoxin exposure. Delayed administration of antibodies to HMG-1 attenuated endotoxin lethality in mice, and administration of HMG-1 itself was lethal. Septic patients who succumbed to infection had increased serum HMG-1 levels, suggesting that this protein warrants investigation as a therapeutic target.read more
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Cellular mechanisms in sepsis.
TL;DR: The fragile balance between negative and positive feedback on the inflammatory mediators is the key factor that modulates the cellular damage and influences the clinical outcome.
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Programmed necrosis, not apoptosis, is a key mediator of cell loss and DAMP-mediated inflammation in dsRNA-induced retinal degeneration
Yusuke Murakami,Hidetaka Matsumoto,Miin Roh,Andrea Giani,Keiko Kataoka,Yuki Morizane,Maki Kayama,Aristomenis Thanos,Shunji Nakatake,Shoji Notomi,Toshio Hisatomi,Yasuhiro Ikeda,Tatsuro Ishibashi,Kip M. Connor,Joan W. Miller,Demetrios G. Vavvas +15 more
TL;DR: It is shown that receptor-interacting protein (RIP) kinase mediates necrosis and enhances inflammation in a mouse model of retinal degeneration induced by dsRNA, a component of drusen in AMD.
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Increased expression of the novel proinflammatory cytokine high mobility group box chromosomal protein 1 in skin lesions of patients with lupus erythematosus.
Karin Popovic,Monica Ek,Alexander Espinosa,Leonid Padyukov,Helena Erlandsson Harris,Marie Wahren-Herlenius,Filippa Nyberg +6 more
TL;DR: The high amount of extracellular HMGB-1 observed in skin lesions indicates that HMGB -1 is involved in the inflammatory process of CLE, underscoring the role of the target organ in the rheumatoid autoimmune inflammatory process.
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Neural regulators of innate immune responses and inflammation.
TL;DR: This work reviews the involvement of the autonomic nervous system in regulating inflammation, with a focus on the vagus nerve, and the clinical implications of the recently discovered anti-inflammatory role of the efferentvagus nerve.
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HMGB1: a signal of necrosis.
TL;DR: High Mobility Group Box 1 protein (HMGB1) is a ubiquitous nuclear protein that is passively released by cells that have died in a traumatic, non-programmed way (necrosis) and is involved in several disorders, including autoimmune ones.
References
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Journal Article
Defective LPS signaling in C3 H/HeJ and C57 BL/10 ScCr mice: Mutations in Tlr4 Gene
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Journal ArticleDOI
Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia
Kevin J. Tracey,Kevin J. Tracey,Yuman Fong,David G. Hesse,Kirk R. Manogue,Annette T. Lee,George C. Kuo,Stephen F. Lowry,Anthony Cerami +8 more
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Journal ArticleDOI
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Hamish R. Michie,Kirk R. Manogue,David R. Spriggs,Arthur Revhaug,S. T. O'Dwyer,Charles A. Dinarello,Anthony Cerami,Sheldon M. Wolff,Douglas W. Wilmore +8 more
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