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KMID : 0614620110580060300
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Korean Journal of Gastroenterology
2011 Volume.58 No. 6 p.300 ~ p.310
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Inflammatory Bowel Diseases and Inflammasome
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Kim Jung-Mogg
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Abstract
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Inflammatory bowel disease (IBD), the most important entities being ulcerative colitis and Crohn’s disease, are chronic, relapsing and remitting inflammatory conditions that result from chronic dysregulation of the mucosal immune system in the intestinal tract. Although the precise pathogenesis of IBD is still incompletely understood, increased levels of proinflammatory cytokines, including interleukin (IL)-1b, IL-18 and tumor necrosis factor-a, are detected in active IBD and correlate with the severity of inflammation, indicating that these cytokines may play a key role in the development of IBD. Recently, the intracellular nucleotide-binding oligomerization domain-like receptor (NLR) family members, including NLRP1, NLRP3, NLRC4 and NLRP6, are emerging as important regulators of intestinal homeostasis. Together, one of those aforementioned molecules or the DNA sensor absent in melanoma 2 (AIM2), apoptosis-associated speck-like protein containing ’a caspase recruitment domain (CARD)’ (ASC) and caspase-1 form a large (＞700 kDa) multi-protein complex called the inflammasome. Stimulation with specific microbial and endogenous molecules triggers inflammasome assembly and caspase-1 activation. Activated caspase-1 leads to the secretion of proinflammatory cytokines, including IL-1b and IL-18, and the promotion of pyroptosis, a form of phagocyte cell death induced by bacterial pathogens, in an inflamed tissue. Therefore, inflammasomes are assumed to mediate host defense against microbial pathogens and gut homeostasis, so that their dysregulation might contribute to IBD pathogenesis. This review focuses on recent advances of the role of NLRP3 inflammasome signaling in IBD pathogenesis. Improving knowledge of the inflammasome could provide insights into potential therapeutic targets for patients with IBD.
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KEYWORD
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Inflammasomes, Inflammatory bowel diseases, Intestinal epithelial cells
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