Zaki Md Hasan, Lamkanfi Mohamed, Kanneganti Thirumala-Devi
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
Drug Discov Today Dis Mech. 2011 Winter;8(3-4):e71-e78. doi: 10.1016/j.ddmec.2011.11.003.
Colorectal cancer is a major health problem in developed countries. Chronic intestinal inflammation predisposes individuals to the development of colorectal cancer. The intracellular NOD-like receptors (NLRs) have emerged as crucial regulators of intestinal inflammation and colorectal tumorigenesis. Activation of several NLRs leads to the formation of a protein complex called the inflammasome, which then triggers the activation of the cysteine protease caspase-1 and the downstream maturation and secretion of the inflammatory cytokines interleukin-1β and -18. Defective inflammasome signaling in the gut contributes to colitis and colorectal tumorigenesis by increasing the permeability of the epithelial barrier, dysregulating the proliferation of epithelial cells, and inducing oncogenic mediators. In this review, we discuss our current knowledge on how the inflammasome protects against colorectal tumorigenesis.
在发达国家,结直肠癌是一个重大的健康问题。慢性肠道炎症使个体易患结直肠癌。细胞内的NOD样受体(NLRs)已成为肠道炎症和结直肠癌发生的关键调节因子。几种NLRs的激活导致形成一种名为炎性小体的蛋白质复合物,进而触发半胱氨酸蛋白酶caspase-1的激活以及炎性细胞因子白细胞介素-1β和-18的下游成熟和分泌。肠道中炎性小体信号传导缺陷通过增加上皮屏障的通透性、失调上皮细胞增殖以及诱导致癌介质,导致结肠炎和结直肠癌发生。在本综述中,我们讨论了目前关于炎性小体如何预防结直肠癌发生的知识。