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
The free radical scavenger edaravone rescues rats from cerebral infarction by attenuating the release of high-mobility group box-1 in neuronal cells.
Kiyoshi Kikuchi,Ko-ichi Kawahara,Salunya Tancharoen,Fumiyo Matsuda,Yoko Morimoto,Takashi Ito,Kamal Krishna Biswas,Kazunori Takenouchi,Naoki Miura,Yoko Oyama,Yuko Nawa,Noboru Arimura,Masahiro Iwata,Yutaka Tajima,Terukazu Kuramoto,Kenji Nakayama,Minoru Shigemori,Yoshihiro Yoshida,Teruto Hashiguchi,Ikuro Maruyama +19 more
TL;DR: A novel neuroprotective mechanism for edaravone is suggested that abrogates the release of high-mobility group box-1 (HMGB1) during a 48-h postischemia/reperfusion period in rats and in oxygen-glucose-deprived PC12 cells.
Journal ArticleDOI
A pilot study to detect high mobility group box 1 and heat shock protein 72 in cerebrospinal fluid of pediatric patients with meningitis
Daolin Tang,Rui Kang,Lizhi Cao,Guo yuan Zhang,Yan Yu,Weimin Xiao,Weimin Xiao,Haichao Wang,Xianzhong Xiao +8 more
TL;DR: CSF levels of HMGB1 and Hsp72 were significantly higher in patients with bacterialMeningitis than those with aseptic meningitis and correlated well with CSF white blood cell counts in patientsWith bacterial (but not aseptic) meneditis.
Patent
Monoclonal antibodies against HMGB1
TL;DR: In various embodiments, the present invention is drawn to antibodies or antigen-binding fragments thereof that bind to a vertebrate high mobility group box (HMGB) polypeptide.
Journal ArticleDOI
Emergence of autoantibodies to HMGB1 is associated with survival in patients with septic shock
Stéphanie Barnay-Verdier,Stéphanie Barnay-Verdier,Stéphanie Barnay-Verdier,Lakhdar Fattoum,Lakhdar Fattoum,Lakhdar Fattoum,Chloé Borde,Chloé Borde,Chloé Borde,Srini V. Kaveri,Srini V. Kaveri,Srini V. Kaveri,Sébastien Gibot,Vincent Maréchal,Vincent Maréchal,Vincent Maréchal +15 more
TL;DR: This study shows that autoantibodies to HMGB1 are produced during sepsis and are associated with a favorable outcome in patients undergoing septic shock.
Journal ArticleDOI
Sputum Biomarkers and the Prediction of Clinical Outcomes in Patients with Cystic Fibrosis
Theodore G. Liou,Frederick R. Adler,Ruth H. Keogh,Yanping Li,Judy L. Jensen,William Robert Walsh,Kristyn A Packer,Teresa Clark,Holly Carveth,Jun Chen,Shaunessy L. Rogers,Christen Lane,Jimmy Moore,Anne Sturrock,Robert Paine,David Cox,John R. Hoidal +16 more
TL;DR: In CF sputum, high HMGB-1 predicts incidence and recurrence of APE and survival, plausibly because it mediates long-term airway inflammation, and high APE-associated GM-CSF identifies patients with large acute declines in FEV1%, possibly providing a laboratory-based objective decision-support tool for determination of an APE diagnosis.
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.