Toll-like receptor expression in crypt epithelial cells, putative stem cells and intestinal myofibroblasts isolated from controls and patients with inflammatory bowel disease

Abstract

The aim of our studies was to investigate the expression of Toll-like receptor (TLR)-2 and TLR-4 (and in some studies TLR-5) in myofibroblasts and small and large intestinal crypt epithelial cells from control patients and those affected by Crohn’s disease and ulcerative colitis. Isolated and disaggregated crypt epithelial cells and monolayers of myofibroblasts were used for studies by reverse transcription–polymerase chain reaction (RT–PCR), real-time RT–PCR, flow cytometry, immunocytochemistry and Western blot analysis. Compared to control cells, crypt epithelial cells isolated from active ulcerative colitis and Crohn’s disease colonic mucosal samples showed significantly higher expression of TLR-2 and TLR-4 transcripts and protein (on the cell surface). There was also enhanced expression of TLR-4 in crypt cells from ileal Crohn’s disease. Expression of TLR-2 and TLR-4 transcripts in crypt epithelial cells isolated from inflamed mucosa of distal ulcerative colitis did not differ significantly from such cells obtained from the normal proximal colon. Crypt epithelial cells with side population characteristics (putative stem cells) also expressed transcripts and protein for TLR-2, TLR-4 and TLR-5. Colonic myofibroblast expression of these TLRs was much weaker than in crypt epithelial cells. In conclusion, enhanced TLR-2 and TLR-4 expression by crypt epithelial cells in active inflammatory bowel disease likely reflects greater ability to respond to microbial products. Results from our studies using mucosal samples from patients with distal ulcerative colitis suggest that the enhanced expression of these TLRs could be constitutive. TLR-2, TLR-4 and TLR-5 expression by stem cells imply ability to respond to distinct bacterial products.

RETRACTED: Antiulcerogenic Activity of Li‐Zhong Decoction on Duodenal Ulcers Induced by Indomethacin in Rats: Involvement of TLR‐2/MyD88 Signaling Pathway

“…TLRs recognize the harmful compounds in the extracellular domain and subsequently transduce signals through downstream molecule MyD88 to stimulate innate immune responses against damages and infections, thus paving way for successful adaptive immunity [39]. Studies in mice have demonstrated that TLR-2, TLR-4, and TLR-5 regulate intestinal epithelial homeostasis and provide protection from injury, such as that mediated by IND, radiation, and dextran sodium sulphate [40]. In this study, we examined levels of TLR-2 and MyD88 mRNA and protein expression in the duodenal mucosa lesions to investigate whether innate immunity had some association with the treatment and prevention of duodenal ulcer.…”

Toll‐like receptors 2 and 4 modulate the contractile response induced by serotonin in mouse ileum: analysis of the serotonin receptors involved

“…Increased expression of TLR4 has been reported in the mucosa of patients with IBD and IBS . Similarly, the expression of TLR2 has been reported to be increased in IBD or remained unchanged in IBD or IBS . However, the role of TLRs in the regulation of intestinal motility is still widely unknown.…”

Pathogenesis of Clostridium difficile Infection and Its Potential Role in Inflammatory Bowel Disease

“…84 Compared with control cells, we have recently reported enhanced expression of TLR2 and TLR4 in crypt epithelial cells isolated from colonic mucosal samples affected by active ulcerative colitis and Crohn's disease. 85 Putative crypt epithelial stem cells also expressed TLR2, TLR4, and TLR5, which may mediate protection against CDI.…”