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
Reads0
Chats0
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
Citations
More filters
Journal ArticleDOI
Increased levels of HMGB1 and pro-inflammatory cytokines in children with febrile seizures.
TL;DR: The data suggest that HMGB1 and the cytokine network may contribute to the generation of febrile seizures in children.
Journal ArticleDOI
Bench-to-bedside review: Latest results in hemorrhagic shock
TL;DR: In this paper, a review points out new therapeutic strategies, namely immunomodulation, cardiovascular maintenance, small volume resuscitation, and so on, that have been introduced in clinics or are in the process of being transferred from bench to bedside.
Journal ArticleDOI
Hepatic DNA deposition drives drug‐induced liver injury and inflammation in mice
Pedro Marques,André G. Oliveira,Rafaela Vaz Sousa Pereira,Bruna Araújo David,Lindisley Ferreira Gomides,Adriana Machado Saraiva,Daniele Araújo Pires,Júlia Tosta Novaes,Daniel O. Patricio,Daniel Cisalpino,Zélia Menezes-Garcia,W. Matthew Leevy,Sarah Chapman,GermánArturo Mahecha,Rafael Elias Marques,Rodrigo Guabiraba,Vicente de Paulo Martins,Danielle G. Souza,Daniel S. Mansur,Mauro Martins Teixeira,M. Fatima Leite,Gustavo B. Menezes +21 more
TL;DR: It is revealed that liver injury due to acetaminophen overdose led to a directional migration of neutrophils to DNA‐rich areas, where they exhibit an active patrolling behavior, which is a novel feature of DILI pathogenesis.
Journal ArticleDOI
Exosomes from Endothelial Progenitor Cells Improve the Outcome of a Murine Model of Sepsis
Yue Zhou,Yue Zhou,Pengfei Li,Andrew J. Goodwin,James A. Cook,Perry V. Halushka,Eugene Chang,Hongkuan Fan +7 more
TL;DR: EPC exosomes prevent microvascular dysfunction and improve sepsis outcomes potentially through the delivery of miR-126, as well as suppressing LPS-induced high mobility group box 1 (HMGB1) and vascular cell adhesion molecule 1 (VCAM1) levels, respectively, in human microv vascular endothelial cells (HMVECs).
Journal ArticleDOI
Regulation of Tumor Progression by Programmed Necrosis.
Su Yeon Lee,Min Kyung Ju,Hyun Min Jeon,Eui Kyong Jeong,Yig Ji Lee,Cho Hee Kim,Hye Gyeong Park,Song Iy Han,Ho Sung Kang +8 more
TL;DR: Snail and Dlx-2, EMT-inducing transcription factors, are responsible for metabolic stress-induced necrosis in tumors and contribute to tumor progression by promoting necrosis and inducing EMT and oncogenic metabolism.
References
More filters
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.