Control of Intestinal Homeostasis, Colitis, and Colitis-Associated Colorectal Cancer by the Inflammatory Caspases

被引：566

作者：

Dupaul-Chicoine, Jeremy ^{[1
]}

Yeretssian, Garabet ^{[2
]}

Doiron, Karine ^{[2
]}

Bergstrom, Kirk S. B. ^{[3
,4
]}

McIntire, Christian R. ^{[1
]}

LeBlanc, Philippe M. ^{[5
]}

Meunier, Charles ^{[1
]}

Turbide, Claire ^{[6
]}

Gros, Philippe ^{[1
,6
]}

Beauchemin, Nicole ^{[1
,6
]}

Vallance, Bruce A. ^{[3
,4
]}

Saleh, Maya ^{[1
,2
]}

机构：

[1] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada

[2] McGill Univ, Dept Med, Montreal, PQ H3G 0B1, Canada

[3] Univ British Columbia, Div Gastroenterol, Vancouver, BC V6T 1Z4, Canada

[4] BC Childrens Hosp, Vancouver, BC V6T 1Z4, Canada

[5] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3A 2B4, Canada

[6] McGill Univ, Goodman Canc Ctr, Montreal, PQ H3A 1A3, Canada

来源：

IMMUNITY | 2010年 / 32卷 / 03期

关键词：

CROHNS-DISEASE; ACTIVATION; IL-18; INTERLEUKIN-18; PROLIFERATION; TUMORIGENESIS; EXPRESSION; INFECTION; IMMUNITY; ADAPTERS;

D O I：

10.1016/j.immuni.2010.02.012

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Inflammatory caspases are essential effectors of inflammation and cell death. Here, we investigated their roles in colitis and colorectal cancer and report a bimodal regulation of intestinal homeostasis, inflammation and tumorigenesis by caspases-1 and -12. Casp1(-/-) mice exhibited defects in mucosa, tissue repair and succumbed rapidly after dextran sulfate sodium administration. This phenotype was rescued by administration of exogenous interleukin-18 and was partially reproduced in mice deficient in the inflammasome adaptor ASC. Casp12(-/-) mice, in which the inflammasome is derepressed, were resistant to acute colitis and showed signs of enhanced repair. Together with their increased inflammatory response, the enhanced repair response of Casp12(-/-) mice rendered them more susceptible to colorectal cancer induced by azoxymethane (AOM)+DSS. Taken together, our results indicate that the inflammatory caspases are critical in the induction of inflammation in the gut after injury, which is necessary for tissue repair and maintenance of immune tolerance.

引用

页码：367 / 378

页数：12

共 33 条

[1]

FLUORESCENT-OLIGONUCLEOTIDE PROBING OF WHOLE CELLS FOR DETERMINATIVE, PHYLOGENETIC, AND ENVIRONMENTAL-STUDIES IN MICROBIOLOGY [J].