Zhonghua yi xue za zhi · 2008
[Signal transduction pathway of colonic Toll-like receptor 4 in patients with irritable bowel syndrome].
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Wang Xue-mei, Liu Yu-lan
Аннотация
OBJECTIVE: 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.
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-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].
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-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.
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-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].
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-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.