Expressions Of TLR4and COX-2, EP2in Colonic Intestinal Epithelium Of Ulcerative Colitis And Relationship Among Them

Objective:Ulcerative colitis is a chronic recurrent non-specific inflammatory bowel disease, which cancer rate is high and is considered a precancerous lesion. Cyclooxygenase (COX), a key enzyme in prostaglandin biosynthesis, are highly expressed in tumors and precancerous lesions, plays an important role in tumorigenesis and development of metastasis. Non-steroidal anti-inflammatory drugs (NSAIDs) can significantly reduce the incidence of colorectal cancer which have been confirmed in animal models and clinical studies. But NSAIDs and COX-2selective inhibitors have significant gastrointestinal and cardiovascular side effects which limit its clinical application. Toll-like receptor4(TLR4) is One of the important endotoxin receptor and an initiating factor to identify and start the inflammatory response, animal experiments confirmed that the TLR4signaling pathway is essential in the formation process of chronic enteritis colorectal cancer, but have not yet carried in the body to observe the relationship between TLR4and COX-2. EP2receptor (prostanoid receptor EP2, EP2) is one of the four receptors of prostaglandin E2(PGE2). It has been confirmed that the EP2receptor is related with occurrence and development of colorectal cance. There is little research on EP2in our country and not yet reported on the EP2receptor and the human colonic inflammation and precancerous lesions. By studing on the expressions of TLR4and COX-2, EP2in colonic intestinal epithelium of ulcerative colitis, we explore the relationships among them in ulcerative colitis mucosal inflammation and hope to provide new ideas for the treatment of ulcerative colitis and cancer chemoprevention.Methods:Thirty-three patients with active UC, eleven patients with remission of UC and twenty-three normal control subjiects were recruited into this trial, and were removed a tissue sample for a biopsy in the rectosigmoid through colonoscopy. At first, the ulcerative colitis disease activity index (UCAI) was calculated and the pathological grades of UC were classified. Then the expressions of TLR4, COX-2and EP2in colonic tissues of the patients with active UC, remission of UC and controls were evaluated by immunohistochemistry. All eligible cases had not used non-steroidal drugs. The treatment of active UC patients is using5-amino salicylic acid4.0g/d oral, and remission UC patients were those who active UC patients had eased for six months after the review colonoscopy and remission treatment is5-amino salicylic acid2.0g/d.Results:1. Active UC group were included in the33cases of patients with UC, UCAI score are active period. Remission UC group were included11patients who UC had been treated and UCAI score<2points. Control group of23patients were healthy persons. The age and gender among active UC, remission of UC and control groups were no significant difference (P>0.05). 2.1mmunohistochemical analysis showed that the expressions of TLR4, COX-2and EP2protein in colonic epithelium and in flammatory cells in the patients with active UC were higher than those in the patients with remission of UC and controls (P<0.01), the difference between UC remission and normal control group about TLR4, COX-2and EP2expression was not statistically significant (P>0.05).3.Among33cases of active UC patients, TLR4and EP2expression of integral increased with the pathological grade, TLR4and EP2expression were positively correlated with pathological grade(P<0.01). COX-2expression was no significant increase with the pathologic grade and was not significantly related with the pathologic grade (P>0.05).4. TLR4, COX-2and EP2protein expression correlation analysis:expression was positively correlated (P<0.01) among the three.Conclusion:The expressions of TLR4and EP2were significantly upregulated in the intestinal epithelium of active UC and positively correlated with the degree of inflammation. These suggest that inhibition of TLR4and EP2receptor may be an active role in the treatment of inflammatory. So TLR4and EP2may be used as a new target for treatment of UC. There were direct correlation among the expressions of TLR4, COX-2and EP2in patients of active UC, prompting TLR4and EP2may play a catalytic role in the progress with chronic inflammation and carcinogenesis process in UC. So inhibiting TLR4and EP2may have a positive effect on the development of chronic colitis-associated colon cancer. This should be confirmed by the observation of the expression of the three in ulcerative colitis-associated colon cancer. Our experiment provides a new approach to chemoprevention of colitis-associated colon cancer.