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

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Abstract
Background NLRP3 inflammasome is a multimolecular cytosol complex that, when activated, contributes to the cleavage of pro-interleukin (IL)-1β to IL-1β. Aims To investigate NLRP3 inflammasome activation in inflammatory bowel disease. Methods 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-1β, IL-6, and TNFα were measured in cell supernatants and concentration of pro-IL-1β was measured in cell lysates. NLRP3 activation was defined as more than 30% increase in IL-1β production after MSU addition. In separate experiments, PBMCs were lysed for RNA isolation transcripts of IL-1β, TNFα, NLRP3, and CASP1 were measured by RT-PCR. DNA was isolated from CD patients for ATG16L1 gene genotyping. Results 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-1β levels were significantly higher in CD patents in comparison with controls (p = 0.032). No difference was detected in the levels of IL-6, TNFα, pro-IL-1β and in the numbers IL-1β, TNFα, NLRP3, and CASP1 transcripts among groups. IL-1β production was similar between carriers of wild-type and of SNP alleles of the rs2241880. Conclusions NLRP3 inflammasome is activated in CD patients and in UC patients with long-standing disease.
Funding Information
  • Merck Sharp and Dohme United Kingdom

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