Relative Research Between Mast Cell And Proteinase Activated Receptor-2,NF-κB Expressed In Intestinal Mucosa Of Patients With Ulcerative Colitis

OBJECTIVE To investigate the expression of proteinase activated receptor-2(PAR-2),NF-κB p65, the change of mast cells(MC) in intestinal mucosa of patients with ulcerative colitis, and the possible roles of PAR-2,NF-κB and MC in the pathogenesis of UC.Methods UC lesion tissues were obtained from consecutive 32 patients undergoing colonoscopy. Patients were also classified histologically as inflammation gradeⅢ,Ⅳ(20 cases)and inflammation gradeⅠ,Ⅱ(12 cases). Normal human colon tissues were obtained from 15 healthy adult volunteers. Semi-quantitative reverse transcription polymerase chain reaction(RT-PCR) were used to determine the expression of PAR-2. Immunohistochemistry was used to determine the expression of PAR-2,NF-κB p65 and the number of MC. Pathological image analysis software was used to investigated the result of semi- immunohistochemistry.Result Expression of PAR-2 in mRNA in mucosa of UC was significantly higher than that of healthy control. Immunohistochemisty showed The number of mast cells with UC was significantly higher than that of the healthy contol group (P<0.01). PAR-2 protein was localized in colonic epithelial cells,crypt surface and inflammatory cells of lamina propria in UC, PAR-2 protein expression was mostly in cytoplasm. The NF-κB p65 expression was significantly stronger in the nuclei than in the cytoplasm. NF-κB p65 expression was found in colonic cryptal epithelial cells, inflammatory cells of lamina propia in UC. No or only weak expression of PAR-2,NF-κB p65 was seen in normal controls. The Patients with inflammation gradeⅢ,Ⅳexhibited significant higher expression of PAR-2,NF-κB p65 and the number of MC than those with inflammation gradeⅠ,Ⅱ(P<0.05). The overexpression of PAR-2 mRNA was positively correlated to the severity of UC (P<0.01). The expression of PAR-2 in protein was positively correlated with the number of mast cell (r=0.78, P<0.01), The expression of PAR-2 in protein was also positively correlated with the NF-κB p65 (r=0.56, P<0.01).Conclusion The occurrence of UC correlates with the increased expression of PAR-2 and number of mast cells. The activation of NF-κB by stimulation of PAR-2 singanaling through Tryptase induced increasing release of inflammatory factors. These results indicated that the activation of PAR-2 through tryptase released from mast cells might be involved in the pathogenesis of UC.