NLRP3 Inflammasome and Inflammatory Bowel Disease

Yu, Zhen; Hu, Zhang

doi:10.3389/fimmu.2019.00276

Cited by 465 publications

(340 citation statements)

References 105 publications

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“…1h). Inflammasome activation functions as an indispensable factor in the pathological process of IBD, contributing to intestinal mucosal inflammation 36 . Interestingly, berberine could suppress the expression level of NLRP3, ASC, and cleaved caspase-1 (Fig.…”

Section: Berberine Alleviated the Inflammatory Injury Of Dssinduced Cmentioning

confidence: 99%

Intervention of oncostatin M-driven mucosal inflammation by berberine exerts therapeutic property in chronic ulcerative colitis

Feng

Chen

et al. 2020

Cell Death Dis

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Ulcerative colitis (UC) is a chronic and etiologically refractory inflammatory gut disorder. Although berberine, an isoquinoline alkaloid, has been revealed to exert protective effects on experimental colitis, the underlying molecular mechanism in chronic intestinal inflammation remains ill-defined. This study was designed to uncover the therapeutic efficacy and immunomodulatory role of berberine in chronic UC. Therapeutic effects of oral administration of berberine were investigated in dextran sodium sulfate (DSS)-induced murine chronic UC and the underlying mechanisms were further identified by si-OSMR transfection in human intestinal stromal cells. Berberine significantly attenuated the experimental symptoms and gut inflammation of chronic UC. Berberine treatment could also maintain the intestinal barrier function and rectify tissue fibrosis. In accordance with infiltrations of antigen-presenting cells (APCs), innate lymphoid cells (ILCs), and activated NK cells in colonic lamina propria, increased expression of OSM and OSMR were observed in the inflamed tissue of chronic UC, which were decreased following berberine treatment. Moreover, berberine inhibited the overactivation of human intestinal stromal cells through OSM-mediated JAK-STAT pathway, which was obviously blocked upon siRNA targeting OSMR. The research provided an infusive mechanism of berberine and illustrated that OSM and OSMR intervention might function as the potential target in chronic UC.

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Section: Berberine Alleviated the Inflammatory Injury Of Dssinduced Cmentioning

confidence: 99%

Intervention of oncostatin M-driven mucosal inflammation by berberine exerts therapeutic property in chronic ulcerative colitis

Feng

Chen

et al. 2020

Cell Death Dis

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“…Interestingly, a number of recent studies have highlighted the importance of NRLP3-dependent mucosal immunity also in inflammatory bowel diseases (IBD), which are frequently associated with cholestatic liver diseases. Moreover, single nucleotide polymorphisms in the NLRP3 gene have been associated with the development of both ulcerative colitis (UC) and Crohn's disease [20,21].…”

Section: Introductionmentioning

confidence: 99%

Gut–Liver Axis and Inflammasome Activation in Cholangiocyte Pathophysiology

Maroni

Ninfole

Pinto

et al. 2020

Cells

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The Nlrp3 inflammasome is a multiprotein complex activated by a number of bacterial products or danger signals and is involved in the regulation of inflammatory processes through caspase-1 activation. The Nlrp3 is expressed in immune cells but also in hepatocytes and cholangiocytes, where it appears to be involved in regulation of biliary damage, epithelial barrier integrity and development of fibrosis. Activation of the pathways of innate immunity is crucial in the pathophysiology of hepatobiliary diseases, given the strong link between the gut and the liver. The liver secretes bile acids, which influence the bacterial composition of the gut microbiota and, in turn, are heavily modified by microbial metabolism. Alterations of this balance, as for the development of dysbiosis, may deeply influence the composition of the bacterial products that reach the liver and are able to activate a number of intracellular pathways. This alteration may be particularly important in the pathogenesis of cholangiopathies and, in particular, of primary sclerosing cholangitis, given its strong association with inflammatory bowel disease. In the present review, we summarize current knowledge on the gut-liver axis in cholangiopathies and discuss the role of Nlrp3 inflammasome activation in cholestatic conditions.

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“…In the present study, we showed that NLRP3 gene promoter site is significantly more methylated in the newly diagnosed jSpA patients, which can be responsible for previously observed expression alteration. While increased expression of the NLRP3 gene has been found in many autoinflammatory diseases, decreased expression has been associated with inflammatory bowel disease (IBD), a disease that shares some striking similarities with jSpA, including the gut dysbiosis [20,21]. The NLRP3 gene has a crucial role in the assembly of the NLRP3 inflammasome, an innate immune sensor that regulates Bdanger^in response to various signals [22].…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Alterations in Juvenile Spondyloarthritis Patients: a Preliminary Study of Selected Genes Promoter Methylation and Silencing

Lamot

Blažeković

Jerčić

et al. 2019

SN Compr. Clin. Med.

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Juvenile spondyloarthritis (jSpA) is a complex disease with both genetic and environmental factors contributing to etiology. Multiple studies have shown that epigenetic mechanisms could link the environment and gene expression and thus provide a potential explanation for external contribution in the pathogenesis of numerous diseases, including rheumatic. Previously obtained gene signatures in jSpA patients revealed distinctive expression of important immune-related genes, though the mechanism(s) responsible for those alterations remained unknown. The purpose of this study was to evaluate the methylation levels of the TLR4, CXCR4, NLRP3, and PTPN12 gene promoter, along with the expression of several non-coding microRNAs (miR-150, miR-146a, miR-181a, and miR-223) in jSpA patients. Peripheral blood samples were obtained from 19 patients newly diagnosed with jSpA according to ILAR classification criteria for enthesitis-related arthritis (ErA) and seven gender-and age-matched subjects without any symptoms or signs of inflammatory disease. The expression of specific microRNAs was analyzed using qRT-PCR with predeveloped microRNA assays. DNA promoter region methylation status of selected genes was assessed by methylated DNA immunoprecipitation (MeDIP) analysis. Fold enrichment of immunoprecipitated DNA differed significantly for NLRP3 promoter site, while the expression analysis of selected microRNAs showed no significant difference in fold change between jSpA patients and healthy controls. The results indicated that epigenetic modifications in the initial phase of the disease could be responsible for some of the expression alterations in jSpA patients. Since NLRP3 has a crucial role in inflammasome assembly and inflammasomes have been shown to shape microbiota, it is tempting to assume that dysbiosis in jSpA patients can at least partially be explained by reduced NLRP3 expression due to hypermethylation, stressing for the first time the epigenetic contribution to jSpA pathophysiology.

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NLRP3 Inflammasome and Inflammatory Bowel Disease

Cited by 465 publications

References 105 publications

Intervention of oncostatin M-driven mucosal inflammation by berberine exerts therapeutic property in chronic ulcerative colitis

Intervention of oncostatin M-driven mucosal inflammation by berberine exerts therapeutic property in chronic ulcerative colitis

Gut–Liver Axis and Inflammasome Activation in Cholangiocyte Pathophysiology

Epigenetic Alterations in Juvenile Spondyloarthritis Patients: a Preliminary Study of Selected Genes Promoter Methylation and Silencing

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