Pellegrini Carolina, Antonioli Luca, Lopez-Castejon Gloria, Blandizzi Corrado, Fornai Matteo
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; Manchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester, UK.
Department of Clinical and Experimental Medicine, University of Pisa , Pisa , Italy.
Front Immunol. 2017 Jan 25;8:36. doi: 10.3389/fimmu.2017.00036. eCollection 2017.
Several lines of evidence point out the relevance of nucleotide-binding oligomerization domain leucine rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome as a pivotal player in regulating the integrity of intestinal homeostasis and shaping innate immune responses during bowel inflammation. Intensive research efforts are being made to achieve an integrated view about the protective/detrimental role of canonical and non-canonical NLRP3 inflammasome activation in the maintenance of intestinal microenvironment integrity. Evidence is also emerging that the pharmacological modulation of NLRP3 inflammasome could represent a promising molecular target for the therapeutic management of inflammatory immune-mediated gut diseases. The present review has been intended to provide a critical appraisal of the available knowledge about the role of canonical and non-canonical NLRP3 inflammasome activation in the dynamic interplay between microbiota, intestinal epithelium, and innate immune system, taken together as a whole integrated network regulating the maintenance/breakdown of intestinal homeostasis. Moreover, special attention has been paid to the pharmacological modulation of NLRP3 inflammasome, emphasizing the concept that this multiprotein complex could represent a suitable target for the management of inflammatory bowel diseases.
多条证据表明，富含亮氨酸重复序列的核苷酸结合寡聚化结构域和含吡啉结构域的蛋白3（NLRP3）炎性小体在调节肠道稳态的完整性以及在肠道炎症期间塑造固有免疫反应中起着关键作用。目前正在进行深入的研究，以全面了解经典和非经典NLRP3炎性小体激活在维持肠道微环境完整性中的保护/有害作用。越来越多的证据表明，NLRP3炎性小体的药理学调节可能是炎症免疫介导的肠道疾病治疗管理中有前景的分子靶点。本综述旨在对经典和非经典NLRP3炎性小体激活在微生物群、肠道上皮和固有免疫系统之间动态相互作用中的作用的现有知识进行批判性评估，并将它们视为一个调节肠道稳态维持/破坏的整体综合网络。此外，特别关注了NLRP3炎性小体的药理学调节，强调了这种多蛋白复合物可能是炎症性肠病管理的合适靶点这一概念。
