To address the role(s), if any, of intestinal epithelial TLR signaling in the pathogenesis of intestinal inflammation, we, and others, have focused on TLR4, the receptor for LPS. Multiple enterocyte cell lines, including (IEC-6) rat enterocytes (27, 73) , primary and cultured (HT-29 and T84) colonocytes (74) (75) (76) and (CMT93) mouse rectal cells (75) express TLR4, the TLR4 adapter protein MD-2, and MyD88. In these cell lines, activation by LPS leads to pro-inflammatory signaling (74-76) as well as changes in cellular processes including proliferation (73) and intracellular TLR4 trafficking (77) . These findings provide evidence that enterocytes may respond directly to LPS via TLR4, yet by no means prove the physiological relevance of such a response. However, clinical significance for TLR signaling in the pathogenesis of intestinal mucosa is suggested as patients with inflammatory bowel disease demonstrate an increase in the expression of TLR4 and TLR2 in the intestinal mucosa (75, 78) , and we have found that TLR4 expression is increased in experimental and human necrotizing enterocolitis (32) . Sensitization of the intestinal mucosa through upregulation of TLRs also occurs in other diseases of intestinal inflammation, including inflammatory bowel disease and intestinal celiac disease (75, (79) (80) (81) , suggesting a potential role in the injury response.