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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Recent insights into the pathogenesis of bacterial sepsis.
TL;DR: This review discusses key components of the pro- and anti-inflammatory response to sepsis, listing potential novel interventional strategies along the way.
Journal ArticleDOI
High Mobility Group Box Protein-1 Correlates with Renal Function in Chronic Kidney Disease (CKD)
Annette Bruchfeld,Annette Bruchfeld,Abdul Rashid Qureshi,Bengt Lindholm,Peter Bárány,Lihong Yang,Peter Stenvinkel,Kevin J. Tracey +7 more
TL;DR: HMGB-1 is elevated significantly in CKD patients and correlates with GFR as well as markers of inflammation and malnutrition, and future studies may delineate whether HMGB- 1 is also a marker of disease activity and severity as a predictor of outcome in CKd.
Journal ArticleDOI
The Alarmin HMGB1 Mediates Age-Induced Neuroinflammatory Priming.
Laura K. Fonken,Matthew G. Frank,Meagan M. Kitt,Heather M. D'Angelo,Diana M. Norden,Michael D. Weber,Ruth M. Barrientos,Jonathan P. Godbout,Linda R. Watkins,Steven F. Maier +9 more
TL;DR: HMGB1 mediates neuroinflammatory priming in the aged brain by blocking the actions of HMGB1 appears to “desensitize” aged microglia to an immune challenge, thereby preventing exaggerated behavioral and neuroinflammatory responses following infection.
Journal ArticleDOI
Translocation of the novel cytokine HMGB1 to the cytoplasm and extracellular space coincides with the peak of clinical activity in experimentally UV-induced lesions of cutaneous lupus erythematosus.
V. Barkauskaite,Monica Ek,Karin Popovic,Helena Erlandsson Harris,Marie Wahren-Herlenius,Filippa Nyberg +5 more
TL;DR: Extracellular and cytoplasmic HMGB1 coincides with the clinically most active phase of photoinduced lesions of cutaneous lupus, and suggests thatHMGB1 is an important factor in the inflammatory autoimmune process of CLE, which may be responsible for the prolonged and sustained inflammation in CLE.
Journal ArticleDOI
HMGB1 and LPS induce distinct patterns of gene expression and activation in neutrophils from patients with sepsis-induced acute lung injury
Eliezer Silva,John J. Arcaroli,Qianbin He,Daiva Svetkauskaite,Christopher D. Coldren,Jerry A. Nick,Katie R. Poch,Jong Sung Park,Anirban Banerjee,Edward Abraham +9 more
TL;DR: It is demonstrated that neutrophils from septic patients are not anergic but instead demonstrate intact activation of NF-κB after exposure to LPS or HMGB1, and also that the patterns of gene expression differ between neutrophil from sepsis-induced acute lung injury stimulated withHMGB1 or LPS.
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.