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

Abstract

To study the expression of TLR4, myeloid differential protein 2 (MD-2), and nuclear factor (NF)-kappa B 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. 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. 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-kappa B of the IBS patients was 83.33%, significantly higher than that of the healthy controls (P = 0.02) and the NF-kappa B 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]. Up-regulation of TLR4 in IBS patients may contribute to occurrence of IBS. There exists the activation of the signal transduction pathway of NF-kappa B 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.