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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Pharmacological Stimulation of the Cholinergic Antiinflammatory Pathway
Thomas R. Bernik,Steven G. Friedman,Mahendar Ochani,Robert DiRaimo,Luis Ulloa,Huan Yang,Samridhi Sudan,Christopher J. Czura,Svetlana Ivanova,Kevin J. Tracey +9 more
TL;DR: Results indicate that stimulation of the cholinergic antiinflammatory pathway by either pharmacological or electrical methods can attenuate the systemic inflammatory response to endotoxin-induced shock.
Journal ArticleDOI
RAGE (Receptor for Advanced Glycation Endproducts), RAGE Ligands, and their role in Cancer and Inflammation
Louis J. Sparvero,Denise Asafu-Adjei,Rui Kang,Daolin Tang,Neilay Amin,Jaehyun Im,Ronnye Rutledge,Brenda Lin,Andrew A. Amoscato,Herbert J. Zeh,Michael T. Lotze +10 more
TL;DR: The Receptor for Advanced Glycation Endproducts [RAGE] is an evolutionarily recent member of the immunoglobulin super-family, encoded in the Class III region of the major histocompatability complex, and sits in a pivotal role, regulating metabolism, inflammation, and epithelial survival in the setting of stress.
Journal ArticleDOI
The interaction between HMGB1 and TLR4 dictates the outcome of anticancer chemotherapy and radiotherapy.
Lionel Apetoh,François Ghiringhelli,Antoine Tesniere,Antoine Tesniere,Antoine Tesniere,Alfredo Criollo,Alfredo Criollo,Alfredo Criollo,Carla Ortiz,Carla Ortiz,Carla Ortiz,Rosette Lidereau,Christophe Mariette,Nathalie Chaput,Nathalie Chaput,Jean-Paul Mira,Suzette Delaloge,Fabrice Andre,Thomas Tursz,Guido Kroemer,Guido Kroemer,Guido Kroemer,Laurence Zitvogel +22 more
TL;DR: It is shown that the release of the high mobility group box 1 protein by dying tumor cells is mandatory to license host dendritic cells (DCs) to process and present tumor antigens, and this knowledge may be clinically exploited to predict the immunogenicity and hence the efficacy of chemotherapeutic regimens.
Journal ArticleDOI
HMGB1, a novel cytokine-like mediator linking acute neuronal death and delayed neuroinflammation in the postischemic brain
Jung-Bin Kim,Joon Sig Choi,Young-Mi Yu,Kihoon Nam,Chun Shu Piao,Seung-Woo Kim,Minhyung Lee,Pyung-Lim Han,Jong-Sang Park,Ja-Kyeong Lee +9 more
TL;DR: It is demonstrated that high-mobility group box 1 (HMGB1), a nonhistone DNA-binding protein, is massively released into the extracellular space immediately after ischemic insult and that it subsequently induces neuroinflammation in the postischemic brain.
Journal ArticleDOI
The N-terminal domain of thrombomodulin sequesters high-mobility group-B1 protein, a novel antiinflammatory mechanism
Kazuhiro Abeyama,David M. Stern,Yuji Ito,Ko-ichi Kawahara,Yasushi Yoshimoto,M. Tanaka,Tomonori Uchimura,Nobuo Ida,Yamazaki Yoshiaki,Shingo Yamada,Yasuhiko Yamamoto,Hiroshi Yamamoto,Satoshi Iino,Noboru Taniguchi,Ikuro Maruyama +14 more
TL;DR: A novel mechanism, i.e., sequestration of mediators, is highlighted, through which an endothelial cofactor, TM, suppresses inflammation quite distinctly from its anticoagulant cofactor activity, thereby preventing the interaction of these mediators with cell surface receptors on effector cells in the vasculature.
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.