Toll-like receptor signaling in intestinal epithelial cells contributes to colonic homoeostasis.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Lee
Jongdae
J
Department of Medicine, University of California San Diego, La Jolla, California 92093, USA.
Mo
Ji-Hun
JH
Shen
Carol
C
Rucker
Adam N
AN
Raz
Eyal
E
D000818:Animals; D004847:Epithelial Cells / Q000378:metabolism*; D041981:Gastrointestinal Tract / Q000166:cytology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D015398:Signal Transduction / Q000502:physiology*; D051193:Toll-Like Receptors / Q000378:metabolism*
D051193:Toll-Like Receptors