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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Expression of cytokine genes during pneumococcal and nontypeable Haemophilus influenzae acute otitis media in the rat.
Åsa Melhus,Allen F. Ryan +1 more
TL;DR: Most of the investigated cytokines are very early markers for AOM and may be involved in initiation of inflammation, but they would be poor targets for pharmacological manipulation since their levels decline before clinical signs appear.
Journal ArticleDOI
Protective effects of curcumin against hepatic fibrosis induced by carbon tetrachloride: modulation of high-mobility group box 1, Toll-like receptor 4 and 2 expression.
TL;DR: It is suggested that curcumin could be an effective agent for preventing liver fibrosis and its mechanism may in part be a consequence of the reduction TLR2, TLR4 and HMGB1 expression.
Journal ArticleDOI
HMGB1, an architectural chromatin protein and extracellular signalling factor, has a spatially and temporally restricted expression pattern in mouse brain.
TL;DR: It is shown here that HMGB1 protein is undetectable in most cells in adult mouse brain, and is present in a subset of brain cells during development, with a very complex temporal, spatial and subcellular expression pattern.
Journal ArticleDOI
The Role of High Mobility Group Box 1 in Innate Immunity
TL;DR: The findings further implicate HMGB1 in lethal inflammatory diseases as a crucial regulator of inflammatory, injurious, and infectious responses.
Journal ArticleDOI
Cannabidiol prevents a post-ischemic injury progressively induced by cerebral ischemia via a high-mobility group box1-inhibiting mechanism.
Kazuhide Hayakawa,Kenichi Mishima,Keiichi Irie,Mai Hazekawa,Shohei Mishima,Masayuki Fujioka,Kensuke Orito,Nobuaki Egashira,Shutaro Katsurabayashi,Kotaro Takasaki,Katsunori Iwasaki,Michihiro Fujiwara +11 more
TL;DR: The results suggest that cannabidiol inhibits monocyte/macropharge expressing HMGB1 followed by preventing glial activation and neurological impairment induced by cerebral ischemia will open new therapeutic possibilities for post-ischemic injury viaHMGB1-inhibiting mechanism.
References
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Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in Tlr4 Gene
Alexander Poltorak,Xiaolong He,Irina Smirnova,Mu Ya Liu,Christophe Van Huffel,Xin Du,Dale Birdwell,E. Alejos,M. Silva,Chris Galanos,Marina Freudenberg,Paola Ricciardi-Castagnoli,Betsy Layton,Bruce Beutler +13 more
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Journal Article
Defective LPS signaling in C3 H/HeJ and C57 BL/10 ScCr mice: Mutations in Tlr4 Gene
Alexander Poltorak,Xiaolong He,Irina Smirnova,Mu Ya Liu,C. Van Huffel,Xin Du,Dale Birdwell,E. Alejos,M. Suva,Chris Galanos,Marina Freudenberg,Paola Ricciardi-Castagnoli,B. Layton,Bruce Beutler +13 more
Journal ArticleDOI
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Kevin J. Tracey,Bruce Beutler,Stephen F. Lowry,James P Merryweather,Stephen D. Wolpe,Ian W. Milsark,Robert J. Hariri,Thomas J. Fahey,Alejandro Zentella,J. D. Albert,G. Tom Shires,Anthony Cerami +11 more
TL;DR: It appears that a single protein mediator (cachectin) is capable of inducing many of the deleterious effects of endotoxin.
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
TL;DR: Protection against shock, vital organ dysfunction, persistent stress hormone release and death was conferred by administration of antibodies 2 h before bacterial infusion, indicating that cachectin is a mediator of fatal bacteraemic shock and suggesting that antibodies against Cachectin offer a potential therapy of life-threatening infection.
Journal ArticleDOI
Detection of circulating tumor necrosis factor after endotoxin administration.
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
TL;DR: It is concluded that the response to endotoxin is associated with a brief pulse of circulating tumor necrosis factor and that the resultant responses are effected through the cyclooxygenase pathway.