Activation of NLRP3 Inflammasome in Inflammatory Bowel Disease: Differences Between Crohn's Disease and Ulcerative Colitis

NLRP3 inflammasome is a multimolecular cytosol complex that, when activated, contributes to the cleavage of pro-interleukin (IL)-1 beta to IL-1 beta. To investigate NLRP3 inflammasome activation in inflammatory bowel disease. Peripheral blood mononuclear cells from Crohn's disease (CD), ulcerative colitis (UC) patients and controls were stimulated with LPS in the absence or presence of MSU. After incubation, concentrations of IL-1 beta, IL-6, and TNF alpha were measured in cell supernatants and concentration of pro-IL-1 beta was measured in cell lysates. NLRP3 activation was defined as more than 30% increase in IL-1 beta production after MSU addition. In separate experiments, PBMCs were lysed for RNA isolation transcripts of IL-1 beta, TNF alpha, NLRP3, and CASP1 were measured by RT-PCR. DNA was isolated from CD patients for ATG16L1 gene genotyping. NLRP3 inflammasome was activated in 60% of CD patients compared to 28.6% of controls (p = 0.042); no significant difference was detected between UC and controls. Among UC patients, NLRP3 activation was associated (p = 0.008) with long-standing disease (> 1.5 years). IL-1 beta levels were significantly higher in CD patents in comparison with controls (p = 0.032). No difference was detected in the levels of IL-6, TNF alpha, pro-IL-1 beta and in the numbers IL-1 beta, TNF alpha, NLRP3, and CASP1 transcripts among groups. IL-1 beta production was similar between carriers of wild-type and of SNP alleles of the rs2241880. NLRP3 inflammasome is activated in CD patients and in UC patients with long-standing disease.