Inflammasomes in Intestinal Inflammation and Cancer

被引:136
作者
Chen, Grace Y. [1 ,2 ]
Nunez, Gabriel [2 ,3 ]
机构
[1] Univ Michigan, Dept Internal Med, Div Hematol & Oncol, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA
基金
美国国家卫生研究院;
关键词
Immune; Regulation; CRC; IBD; Microbiota; DEXTRAN SULFATE SODIUM; INDUCED EXPERIMENTAL COLITIS; NF-KAPPA-B; III SECRETION APPARATUS; ANTHRAX LETHAL TOXIN; NOD-LIKE RECEPTORS; CD4(+) T-CELLS; NLRP3; INFLAMMASOME; CASPASE-1; ACTIVATION; CROHNS-DISEASE;
D O I
10.1053/j.gastro.2011.10.002
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Inflammasomes are multi-protein complexes that mediate activation of caspase-1, which promotes secretion of the proinflammatory cytokines interleukin-1 beta and interleukin-18 and pyroptosis, a form of phagocyte cell death induced by bacterial pathogens. Members of the Nod-like receptor family (including Nlrp1, Nlrp3, and Nlrc4), the DNA sensor Aim2, the adaptor apoptosis-associated speck-like protein (ASC), and pro-caspase-1 are important components of inflammasomes. Stimulation with specific microbial and endogenous molecules leads to inflammasome assembly and caspase-1 activation. Inflammasomes are believed to mediate host defense against microbial pathogens and tissue homeostasis within the intestine, and their dysregulation might contribute to inflammatory diseases and intestinal cancer. Improving our understanding of inflammasome signaling pathways could provide insights into the pathogenesis of many gastrointestinal disorders and the development of therapeutic targets and approaches to treat diseases such as inflammatory bowel diseases and gastrointestinal cancers.
引用
收藏
页码:1986 / 1999
页数:14
相关论文
共 115 条
[21]   Protection of the intestinal mucosa by intraepithelial γδ T cells [J].
Chen, YP ;
Chou, K ;
Fuchs, E ;
Havran, WL ;
Boismenu, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (22) :14338-14343
[22]  
COOPER HS, 1993, LAB INVEST, V69, P238
[23]   Inflammation and cancer [J].
Coussens, LM ;
Werb, Z .
NATURE, 2002, 420 (6917) :860-867
[24]   Structure and Interdomain Dynamics of Apoptosis-associated Speck-like Protein Containing a CARD (ASC) [J].
de Alba, Eva .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (47) :32932-32941
[25]   Inflammasome activation and IL-1β and IL-18 processing during infection [J].
de Veerdonk, Frank L. van ;
Netea, Mihai G. ;
Dinarello, Charles A. ;
Joosten, Leo A. B. .
TRENDS IN IMMUNOLOGY, 2011, 32 (03) :110-116
[26]   Plant NBS-LRR proteins in pathogen sensing and host defense [J].
DeYoung, Brody J. ;
Innes, Roger W. .
NATURE IMMUNOLOGY, 2006, 7 (12) :1243-1249
[27]   Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica [J].
Dostert, Catherine ;
Petrilli, Virginie ;
Van Bruggen, Robin ;
Steele, Chad ;
Mossman, Brooke T. ;
Tschopp, Jurg .
SCIENCE, 2008, 320 (5876) :674-677
[28]  
Dove WF, 1997, CANCER RES, V57, P812
[29]   Control of Intestinal Homeostasis, Colitis, and Colitis-Associated Colorectal Cancer by the Inflammatory Caspases [J].
Dupaul-Chicoine, Jeremy ;
Yeretssian, Garabet ;
Doiron, Karine ;
Bergstrom, Kirk S. B. ;
McIntire, Christian R. ;
LeBlanc, Philippe M. ;
Meunier, Charles ;
Turbide, Claire ;
Gros, Philippe ;
Beauchemin, Nicole ;
Vallance, Bruce A. ;
Saleh, Maya .
IMMUNITY, 2010, 32 (03) :367-378
[30]   NLRP6 Inflammasome Regulates Colonic Microbial Ecology and Risk for Colitis [J].
Elinav, Eran ;
Strowig, Till ;
Kau, Andrew L. ;
Henao-Mejia, Jorge ;
Thaiss, Christoph A. ;
Booth, Carmen J. ;
Peaper, David R. ;
Bertin, John ;
Eisenbarth, Stephanie C. ;
Gordon, Jeffrey I. ;
Flavell, Richard A. .
CELL, 2011, 145 (05) :745-757