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
LPS Induces Active HMGB1 Release From Hepatocytes Into Exosomes Through the Coordinated Activities of TLR4 and Caspase-11/GSDMD Signaling
Wenbo Li,Meihong Deng,Patricia Loughran,Mu-qing Yang,Mu-qing Yang,Minjie Lin,Minjie Lin,Chenxuan Yang,Chenxuan Yang,Wentao Gao,Shuqing Jin,Shuqing Jin,Shilai Li,Shilai Li,Jingjing Cai,Jingjing Cai,Ben Lu,Timothy R. Billiar,Melanie J. Scott +18 more
TL;DR: A novel mechanism that TLR4 signaling results in an increase in caspase-11 expression, as well as increased exosome release, while casp enzyme-11/GsdmD activation/cleavage leads to accumulation of HMGB1 in the cytoplasm through a process associated with the release of calcium from the endoplasmic reticulum and camkkβ activation is provided.
Journal ArticleDOI
High-mobility group box 1 contributes to lethality of endotoxemia in heme oxygenase-1-deficient mice
Rina Takamiya,Chi Chih Hung,Sean Hall,Koichi Fukunaga,Takashi Nagaishi,Takashi Nagaishi,Toshitaka Maeno,Caroline A. Owen,Alvaro Macias,Laura E. Fredenburgh,Akitoshi Ishizaka,Richard S. Blumberg,Rebecca M. Baron,Mark A. Perrella +13 more
TL;DR: Exaggerated circulating levels of HMGB1 contribute to endotoxin-induced mortality in the absence of heme oxygenase (HO)-1, which is suggested to contribute to the pathobiology of endotoxemia.
Journal ArticleDOI
Ligand recognition specificity of leukocyte integrin αMβ2 (Mac-1, CD11b/CD18) and its functional consequences.
Nataly P. Podolnikova,Andriy V. Podolnikov,Thomas A. Haas,Valeryi K. Lishko,Tatiana P. Ugarova +4 more
TL;DR: In this paper, the α(M)I-domain recognition motif was identified as a small core consisting of basic amino acids flanked by hydrophobic residues, and the peptides selected by phage display conformed to a similar pattern.
Book
Annual Update in Intensive Care and Emergency Medicine 2014
TL;DR: It is necessary to select patients suitable for admission to the ICU on a case-by-case basis on the basis of prior history, prior to admission, and on the day of admission.
Journal ArticleDOI
Potential protective mechanisms of green tea polyphenol EGCG against COVID-19
TL;DR: In this paper, the potential protective effects of (−)-epigallocatechin-3-gallate (EGCG), a major constituent of green tea, against COVID-19 was discussed.
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.