NLRP3 Inflammasome-Mediated Inflammatory Process In Patients With Irritable Bowel Syndrome

Objective:Detect changes of NLRP3 signal transduction pathway to analyze NLRP3-mediated IL-lbeta release inflammatory process in the irritable bowel syndrome pathogenesis.Methods:Sigmoid colon mucosa specimens were collection from 36 patients with IBS (16 cases of diarrhea IBS, constipation IBS in 20 cases) and 18 normal controls,18 patients with ulcerative colitis (positive control). Immunohistochemical staining determined the NLRP3 expression of colonic mucosa and we applied ELISA assay to detact caspase-1 and IL-lbeta levels of the mucosa.Result:Caspase-1 and IL-lbeta levels of sigmoid colon mucosa increased in patients with irritable bowel syndrome, but no statistical significance,In the NLRP3 Immunohistochemistry staining,the positive cells number and the mean density of the colon interstitial mucosa was higher in the IBS group than the normal control group.IL-lbeta levels and NLRP3 expression of interstitial colon,including positive cells and mean density, had good correlation in the normal control group. IL-1beta levels and NLRP3 expression of interstitial colon had poor correlation in the IBS group.Conclusions:NLRP3 expression of the sigmoid colon interstitial mucosa was higher in the IBS group than the normal control group. Caspase-1 and IL-lbeta levels of sigmoid colon mucosa increased iust in some patients with irritable bowel syndrome.Compared with normal controls,the expression of NLRP3 in colon interstitial didn't match the colon IL-lbeta levels in patients with irritable bowel syndrome. This suggests that NLRP3 expression of monocytes and macrophages was higher in the IBS group,while NLRP3 inflammasome only activated in part of the patients.Increased expression of NLRP3 in monocytes and macrophages improved the sensitivity to the stimulation of the pathogenic microorganisms. So when the pathogenic microorganisms interact with the intestinal mucosa,the NLRP3 inflammasome mediated synthesis and secretion of IL-lbeta significantly increasd in patients with IBS.