当前位置： SCI文献检索 > Mucosal Immunology期刊下所有文献 > A critical role for cellular inhibitor of protein 2 (cIAP2) in colitis-associated colorectal cancer and intestinal homeostasis mediated by the inflammasome and survival pathways.

A critical role for cellular inhibitor of protein 2 (cIAP2) in colitis-associated colorectal cancer and intestinal homeostasis mediated by the inflammasome and survival pathways.

Abstract：

:Cellular inhibitors of apoptosis proteins (cIAPs) are critical arbiters of cell death and key mediators of inflammation and innate immunity. cIAP2 is frequently overexpressed in colorectal cancer and in regenerating crypts of ulcerative colitis patients. However, its corresponding functions in intestinal homeostasis and underlying mechanisms in disease pathogenesis are poorly understood. We found that mice deficient in cIAP2 exhibited reduced colitis-associated colorectal cancer tumor burden but, surprisingly, enhanced susceptibility to acute and chronic colitis. The exacerbated colitis phenotype of cIAP2-deficient mice was mediated by increased cell death and impaired activation of the regenerative inflammasome-interleukin-18 (IL-18) pathway required for tissue repair following injury. Accordingly, administration of recombinant IL-18 or pharmacological inhibition of caspases or the kinase RIPK1 protected cIAP2-deficient mice from colitis and restored intestinal epithelial barrier architecture. Thus, cIAP2 orchestrates intestinal homeostasis by exerting a dual function in suppressing cell death and promoting intestinal epithelial cell proliferation and crypt regeneration.

journal_name

Mucosal Immunol

journal_title

Mucosal immunology

authors

Dagenais M,Dupaul-Chicoine J,Champagne C,Skeldon A,Morizot A,Saleh M

doi

10.1038/mi.2015.46

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

146-58

issue

1

eissn

1933-0219

issn

1935-3456

pii

mi201546

journal_volume

9

pub_type

杂志文章

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