[An investigation of signal transduction pathway of colonic mucosal toll-like receptor 4 in patients with diarrhea-irritable bowel syndrome].
OBJECTIVE
To study the expressions of TLR4, CD14, MD-2 and NF-κB in colonic mucosa in patients with diarrhea-irritable bowel syndrome (IBS-D), and compared with normal subjects. The purpose of this study is to explore the role of TLR4 and TLR4 signal transduction pathway in the pathogenesis of IBS-D.


METHODS
The expressions of TLR4, CD14, MD-2 and NF-κB in colon mucosa were examined by immunohistochemistry (IHC) in 30 IBS-D patients and 12 healthy volunteers separately. The average absorbance (A value) of TLR4 was analyzed. The positive expression rates of CD14, MD-2 and NF-κB of colonic mucosa were studied.


RESULTS
Compared with healthy controls, significant upregulation of TLR4 expression relative to controls was found in colon mucosa of IBS-D.A value of TLR4 in IBS-D was significantly higher (0.3971±0.0996 vs 0.3044±0.0481). The positive rate and intensity of NF-κB in IBS-D were significantly higher than those in healthy. The number of positive cells of MD-2 showed significant increase in lamina propria of IBS-D against controls. The percent of CD14 positive was upregulated in lamina propria in IBS-D. The expressions of MD-2 and CD14 in intestine epithelial cell were low or negative.


CONCLUSIONS
There is the activation of the signal transduction pathway of TLR4/NF-κB in the colonic mucosa of patients with IBS-D. Up-regulated expression of TLR4 in IBS patients suppose that it might contribute to occurrence of IBS-D.
Wang
Xue-mei
XM
Department of Gastroenterology, Peking University People's Hospital, Beijing 100044, China.
Liu
Yu-lan
YL
D000328:Adult; D016022:Case-Control Studies; D003967:Diarrhea / Q000378:metabolism*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D043183:Irritable Bowel Syndrome / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4