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[Signal transduction pathway of colonic Toll-like receptor 4 in patients with irritable bowel syndrome.]

Zhonghua Yi Xue Za Zhi. 2008 Dec 30;88(48):3415-7

Authors: Wang XM, Liu YL

OBJECTIVE: To study the expression of TLR4, myeloid differential protein 2 (MD-2), and nuclear factor (NF)-kappaB in the colonic mucosa with irritable bowel syndrome (IBS) in patients and to explore the role of TLR4 in the pathogenesis of IBS and TLR4 signal transduction pathway. METHODS: Immunohistochemistry was used to detect the expression of TLR4, MD-2, and NF-kappaB in the colon mucosa specimens of 30 patients with diarrhea-predominant irritable bowel syndrome (IBS-D) and 12 healthy volunteers obtained by colonoscopy. RESULTS: The A value of TLR4 in the IBS specimens was (0.40 +/- 0.10), significantly higher than that of the specimens from the controls [(0.30 +/- 0.05), P = 0.001]. MD-2 expression was not seen in the intestinal epithelial cells (IECs) of 10 healthy controls and was lowly expressed in the sigmoid mucosa of 2 of the 12 healthy controls; and was lowly expressed in 4 of the IBS patients and not expressed in 26 of the 30 IBS patients. The mean number of MD-2 positive cells in the IBS patients was 2.26 (0.80 - 4.73)/view field, significantly higher than that of the healthy controls [0.90 (0.56 - 1.33)/view field, P = 0.003]. The positive rate of NF-kappaB of the IBS patients was 83.33%, significantly higher than that of the healthy controls (P = 0.02) and the NF-kappaB intensity of the IBS patients of the A value was (0.31 +/- 0.04), significantly higher than that of the healthy controls [(0.25 +/- 0.04), P = 0.003]. CONCLUSION: Up-regulation of TLR4 in IBS patients may contribute to occurrence of IBS. There exists the activation of the signal transduction pathway of NF-kappaB in the colonic mucosa of IBS patients, which suggested that inflammation participates in pathogenesis of IBS. The low and negative expression of MD-2 may contribute to the tolerance with the intestinal commensal bacteria.

PMID: 19159572 [PubMed - in process]

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