HMGB1 and RAGE in Inflammation and Cancer

被引:1156
作者
Sims, Gary P. [1 ]
Rowe, Daniel C. [1 ]
Rietdijk, Svend T. [2 ]
Herbst, Ronald [1 ]
Coyle, Anthony J. [1 ]
机构
[1] Medimmune Inc, Dept Resp Inflammat & Autoimmune Dis, Gaithersburg, MD 20878 USA
[2] Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol & Hepatol, NL-1105 AZ Amsterdam, Netherlands
来源
ANNUAL REVIEW OF IMMUNOLOGY, VOL 28 | 2010年 / 28卷
关键词
high mobility group box 1; necrosis; S100; proteins; Toll-like receptors; tolerance; autoimmune disease; GLYCATION END-PRODUCTS; MOBILITY GROUP BOX-1; PLASMACYTOID DENDRITIC CELLS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; MELANOMA INHIBITORY-ACTIVITY; MOLECULAR-PATTERN MOLECULES; LIVER ISCHEMIA-REPERFUSION; CHROMATIN PROTEIN HMGB1; DNA-BINDING PROTEINS; NF-KAPPA-B;
D O I
10.1146/annurev.immunol.021908.132603
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The immune system has evolved to respond not only to pathogens, but also to signals released from dying cells. Cell death through necrosis induces inflammation, whereas apoptotic cell death provides an important signal for tolerance induction. High mobility group box 1 (HMGB1) is a DNA-binding nuclear protein, released actively following cytokine stimulation as well as passively during cell death; it is the prototypic damage-associated molecular pattern (DAMP) molecule and has been implicated in several inflammatory disorders. HMGB1 can associate with other molecules, including TLR ligands and cytokines, and activates cells through the differential engagement of multiple surface receptors including TLR2, TLR4, and RAGE. RAGE is a multiligand receptor that binds structurally diverse molecules, including not only HMGB1, but also S100 family members and amyloid-beta. RAGE activation has been implicated in sterile inflammation as well as in cancer, diabetes, and Alzheimer's disease. While HMGB1 through interactions with TLRs may also be important, this review focuses on the role of the HMGB1-RAGE axis in inflammation and cancer.
引用
收藏
页码:367 / 388
页数:22
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