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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Cytokine-like activities of some aminoacyl-tRNA synthetases and auxiliary p43 cofactor of aminoacylation reaction and their role in oncogenesis.
Serhiy S Ivakhno,A. I. Kornelyuk +1 more
TL;DR: Moonlighting proteins are represented by enzymes and cofactors of aminoacylation reactions, by means of which tRNAs are attached to their cognate amino acids, which play important role in cancer progression, modulating tumor angiogenesis and its escape from surveillance by immune system.
Journal ArticleDOI
The HMGB1-RAGE axis mediates traumatic brain injury-induced pulmonary dysfunction in lung transplantation.
Daniel J. Weber,Adam S.A. Gracon,Matthew S. Ripsch,Amanda Fisher,Bo M. Cheon,Pankita H. Pandya,Ragini Vittal,Maegan L. Capitano,Youngsook Kim,Yohance M. Allette,Amanda A. Riley,Brian P. McCarthy,Paul R. Territo,Gary D. Hutchins,Hal E. Broxmeyer,George E. Sandusky,Fletcher A. White,David S. Wilkes +17 more
TL;DR: Data suggest that the HMGB1-RAGE axis plays a role in the mechanism by which TBI induces lung dysfunction and that targeting this pathway before transplant may improve recipient outcomes after lung transplantation.
Journal ArticleDOI
The Acute Inflammatory Response in Trauma / Hemorrhage and Traumatic Brain Injury: Current State and Emerging Prospects
Rajaie Namas,Ali Ghuma,L Hermus,Ruben Zamora,David O. Okonkwo,Timothy R. Billiar,Yoram Vodovotz +6 more
TL;DR: Novel approaches, including those from the field of systems biology, may yield therapeutic breakthroughs in T/HS and TBI in the near future.
Journal ArticleDOI
High mobility group box 1 (HMGB1).
Huan Yang,Kevin J. Tracey +1 more
TL;DR: High mobility group box 1 is an extremely abundant protein that is widely distributed in all mammalian tissues; HMGB1like proteins are also found in yeast, bacteria, and plants.
Journal ArticleDOI
Ghrelin protects mice against endotoxemia-induced acute kidney injury
TL;DR: Ghrelin offered significant protection against endotoxemia-induced AKI and was associated with an inhibition of the proinflammatory cytokines, which was of particular importance was the suppression of TNF-alpha both in the circulation and kidney tissues.
References
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Journal ArticleDOI
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
TL;DR: The mammalian Tlr4 protein has been adapted primarily to subserve the recognition of LPS and presumably transduces the LPS signal across the plasma membrane.
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
Shock and tissue injury induced by recombinant human cachectin.
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.