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High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal.
Michael T. Lotze,Kevin J. Tracey +1 more
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TLDR
These features of HMGB1 are discussed and recent advances that have led to the preclinical development of therapeutics that modulateHMGB1 release and activity are summarized.Abstract:
High-mobility group box 1 protein (HMGB1), which previously was thought to function only as a nuclear factor that enhances transcription, was recently discovered to be a crucial cytokine that mediates the response to infection, injury and inflammation. These observations have led to the emergence of a new field in immunology that is focused on understanding the mechanisms of HMGB1 release, its biological activities and its pathological effects in sepsis, arthritis, cancer and other diseases. Here, we discuss these features of HMGB1 and summarize recent advances that have led to the preclinical development of therapeutics that modulate HMGB1 release and activity.read more
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Pattern Recognition Receptors and Inflammation
Osamu Takeuchi,Shizuo Akira +1 more
TL;DR: The role of PRRs, their signaling pathways, and how they control inflammatory responses are discussed.
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Taking dendritic cells into medicine
TL;DR: Some medical implications of DC biology that account for illness and provide opportunities for prevention and therapy are presented.
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The Beclin 1 network regulates autophagy and apoptosis
TL;DR: New findings regarding the organization and function of the Beclin 1 network in cellular homeostasis are summarized, focusing on the cross-regulation between apoptosis and autophagy.
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Gender Disparity in Liver Cancer Due to Sex Differences in MyD88-Dependent IL-6 Production
Willscott E. Naugler,Toshiharu Sakurai,Sunhwa Kim,Shin Maeda,Kyounghyun Kim,Ahmed M. Elsharkawy,Ahmed M. Elsharkawy,Michael Karin +7 more
TL;DR: It is proposed that estrogen-mediated inhibition of IL-6 production by KCs reduces liver cancer risk in females, and these findings may be used to prevent HCC in males.
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How dying cells alert the immune system to danger
Hajime Kono,Kenneth L. Rock +1 more
TL;DR: Current knowledge of cell death and repair processes in the host and their importance to host defence and disease pathogenesis has only been appreciated relatively recently is reviewed.
References
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Journal ArticleDOI
Release of chromatin protein HMGB1 by necrotic cells triggers inflammation
TL;DR: It is reported that Hmgb1-/- necrotic cells have a greatly reduced ability to promote inflammation, which proves that the release of HMGB1 can signal the demise of a cell to its neighbours, and cells undergoing apoptosis are programmed to withhold the signal that is broadcast by cells that have been damaged or killed by trauma.
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
TL;DR: 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.
Journal ArticleDOI
Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs
TL;DR: It is shown that human dendritic cells, but not macrophages, efficiently present antigen derived from apoptotic cells, stimulating class I-restricted CD8+ CTLs, suggesting a mechanism by which potent APCs acquire antigens from tumours, transplants, infected cells, or even self-tissue, for stimulation or tolerization of C TLs.
Journal ArticleDOI
High-Dose Recombinant Interleukin 2 Therapy for Patients With Metastatic Melanoma: Analysis of 270 Patients Treated Between 1985 and 1993
Michael B. Atkins,Michael T. Lotze,Janice P. Dutcher,Richard I. Fisher,Geoffrey R. Weiss,Kim Margolin,Jeff Abrams,M. Sznol,David Parkinson,Michael Hawkins,Carolyn Paradise,Lori Kunkel,Steven A. Rosenberg +12 more
TL;DR: High-dose IL-2 treatment seems to benefit some patients with metastatic melanoma by producing durable CRs or PRs and should be considered for appropriately selected melanoma patients.
Journal ArticleDOI
Molecular identification of a danger signal that alerts the immune system to dying cells
TL;DR: Uric acid stimulates dendritic cell maturation and, when co-injected with antigen in vivo, significantly enhances the generation of responses from CD8+ T cells, and have important implications for vaccines, autoimmunity and inflammation.
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