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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A novel pathway of HMGB1-mediated inflammatory cell recruitment that requires Mac-1-integrin.
Valeria V. Orlova,Eun-Young Choi,Changping Xie,Emmanouil Chavakis,Angelika Bierhaus,Eveliina Ihanus,Christie M. Ballantyne,Carl G. Gahmberg,Marco Bianchi,Peter P. Nawroth,Triantafyllos Chavakis +10 more
TL;DR: A novel HMGB1‐dependent pathway for inflammatory cell recruitment and activation that requires the functional interplay between Mac‐1 and RAGE is described here.
Journal ArticleDOI
Regulated expression and subcellular localization of HMGB1, a chromatin protein with a cytokine function
TL;DR: Evidence is provided that, far from being housekeeping, the HMGB1 gene is tightly regulated, which can have implications for therapeutic intervention on inflammatory diseases as well as cancer.
Journal ArticleDOI
Hepatic Ischemia/Reperfusion Injury Involves Functional TLR4 Signaling in Nonparenchymal Cells
Allan Tsung,Rosemary A. Hoffman,Kunihiko Izuishi,Nathan D. Critchlow,Atsunori Nakao,Meagan H. Chan,Michael T. Lotze,David A. Geller,Timothy R. Billiar +8 more
TL;DR: It is demonstrated that TLR4 engagement on actively phagocytic nonparenchymal cells such as Kupffer cells is required for warm I/R-induced injury and inflammation in the liver.
Journal ArticleDOI
Prevalence and Clinical Significance of Sterile Intra‐amniotic Inflammation in Patients with Preterm Labor and Intact Membranes
Roberto Romero,Jezid Miranda,Jezid Miranda,Tinnakorn Chaiworapongsa,Tinnakorn Chaiworapongsa,Steven J. Korzeniewski,Steven J. Korzeniewski,Piya Chaemsaithong,Piya Chaemsaithong,Francesca Gotsch,Zhong Dong,Zhong Dong,Ahmed I. Ahmed,Ahmed I. Ahmed,Bo Hyun Yoon,Sonia S. Hassan,Sonia S. Hassan,Chong Jai Kim,Chong Jai Kim,Lami Yeo,Lami Yeo +20 more
TL;DR: The relationship between amniotic fluid concentrations of high mobility group box‐1 (HMGB1) and the interval from amniocentesis to delivery in patients with sterile intra‐amniotic inflammation is examined.
Journal ArticleDOI
Contributions of high mobility group box protein in experimental and clinical acute lung injury
Hiroshi Ueno,Tomoyuki Matsuda,Satoru Hashimoto,Fumimasa Amaya,Yoshihiro Kitamura,Masaki Tanaka,Atsuko Kobayashi,Ikuro Maruyama,Shingo Yamada,Naoki Hasegawa,Junko Soejima,Hidefumi Koh,Akitoshi Ishizaka +12 more
TL;DR: Examination of the putative role of high mobility group box (HMGB) protein in the pathogenesis of acute lung injury suggests that it also plays a physiologic role in the lung and extracellular HMGB1 expression in normal airways is noteworthy and suggests this protein may play a key role in clinical and experimental ALI.
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
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Journal Article
Defective LPS signaling in C3 H/HeJ and C57 BL/10 ScCr mice: Mutations in Tlr4 Gene
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Journal ArticleDOI
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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.