Lee Jongdae, Mo Ji-Hun, Shen Carol, Rucker Adam N, Raz Eyal
Department of Medicine, University of California San Diego, La Jolla, California 92093, USA.
Curr Opin Gastroenterol. 2007 Jan;23(1):27-31. doi: 10.1097/MOG.0b013e3280118272.
Since intestinal epithelium expresses Toll-like receptors, it was suggested that the intestinal epithelium is actively involved in the maintenance of colonic homeostasis. Here we describe our recent findings, which support an active contribution of colonic epithelium to intestinal homeostasis via a unique activation of epithelial TLR9.
Recent data indicate that stimulation of Toll-like receptors by intestinal microbiota supports colonic homeostasis. Several Toll-like receptors are expressed in intestinal epithelium. TLR9, an intracellular protein in immune cells, is expressed on the cell surfaces of intestinal epithelium, both on the apical and the basolateral membrane. TLR9 signaling varies in a domain-specific manner; whereas JNK is activated by TLR9 ligand both apically or basolaterally, NF-kappaB is activated only via basolateral stimulation. In apical TLR9 stimulation, IkappaB is phosphorylated and ubiquitinated but is not degraded, and NF-kappaB-dependent inflammatory signals are not transduced. Stimulation of apical TLR9 compromises the inflammatory cascade induced basolaterally by several other Toll-like receptor ligands, suggesting that apical exposure to luminal microbial DNA restrains intestinal inflammation.
These data indicate that certain luminal bacterial products support colonic homeostasis via activation of epithelial Toll-like receptors. The role of epithelial Toll-like receptor expression and activation in the pathogenesis of human inflammatory bowel disease is yet to be explored.
由于肠道上皮表达Toll样受体,有人提出肠道上皮积极参与结肠内环境稳态的维持。在此,我们描述我们最近的发现,这些发现支持结肠上皮通过独特激活上皮TLR9对肠道内环境稳态做出积极贡献。
最近的数据表明,肠道微生物群对Toll样受体的刺激支持结肠内环境稳态。几种Toll样受体在肠道上皮中表达。TLR9是免疫细胞中的一种细胞内蛋白,在肠道上皮细胞表面表达,包括顶端和基底外侧膜。TLR9信号传导以结构域特异性方式变化;虽然顶端或基底外侧的TLR9配体均可激活JNK,但NF-κB仅通过基底外侧刺激被激活。在顶端TLR9刺激中,IκB被磷酸化和泛素化,但不被降解,且不转导NF-κB依赖性炎症信号。顶端TLR9的刺激会损害由其他几种Toll样受体配体在基底外侧诱导的炎症级联反应,这表明顶端暴露于管腔微生物DNA可抑制肠道炎症。
这些数据表明,某些管腔细菌产物通过激活上皮Toll样受体来支持结肠内环境稳态。上皮Toll样受体表达和激活在人类炎症性肠病发病机制中的作用尚待探索。