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Mucosal Immunol. 2014 Sep;7(5):1139-50. doi: 10.1038/mi.2014.1. Epub 2014 Jan 29.

Inflammasome activation has an important role in the development of spontaneous colitis.

Author information

1
1] Department of Microbiology and Immunology, Medical University of South Carolina (MUSC), Charleston, South Carolina, USA [2] Hollings Cancer Center, Medical University of South Carolina (MUSC), Charleston, South Carolina, USA.
2
1] Department of Microbiology and Immunology, Medical University of South Carolina (MUSC), Charleston, South Carolina, USA [2] Department of Hepatobiliary Surgery, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People's Republic of China.
3
Department of Pathology and Laboratory Medicine, Medical University of South Carolina (MUSC), Charleston, South Carolina, USA.

Abstract

Inflammatory bowel disease (IBD) is characterized for dysregulated intestinal inflammation. Conflicting reports have shown that activation of inflammasome could promote or decrease intestinal inflammation in an acute colitis model, whereas the involvement of inflammasome activation in chronic colitis is poorly understood. In this study, we investigated the role of inflammasome activation in the development of chronic intestinal inflammation by utilizing interleukin-10 (IL-10) knockout (KO) mouse as an animal model, which develops chronic colitis resembling human IBD. We demonstrate the causative link between inflammasome activation and the development of chronic intestinal inflammation. Our results show that mature IL-1β protein levels were significantly increased in all colon sections from IL-10-deficient mice compared with that of wild-type mice. We found that inhibition of inflammasome activities with IL-1 receptor antagonist or caspase-1 inhibitors suppressed IL-1β and IL-17 production from inflamed colon explants. Furthermore, blocking inflammasome activation with caspase-1 inhibitor in vivo significantly ameliorated the spontaneous colitis in IL-10 KO mice. Taken together, these observations demonstrate that inflammasome activation promotes the development of chronic intestinal inflammation.

PMID:
24472848
PMCID:
PMC4115056
DOI:
10.1038/mi.2014.1
[Indexed for MEDLINE]
Free PMC Article

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