NLRP3 inflammasome has a protective effect against oxazolone-induced colitis: a possible role in ulcerative colitis

Itani, Shigehiro; Watanabe, Toshio; Nadatani, Yuji; Sugimura, Naoki; Shimada, Sunao; Takeda, Shogo; Otani, Koji; Hosomi, Shuhei; Nagami, Yasuaki; Tanaka, Fumio; Kamata, Noriko; Yamagami, Hirokazu; Tanigawa, Tetsuya; Shiba, Masatsugu; Tominaga, Kazunari; Fujiwara, Yasuhiro; Arakawa, Tetsuo

doi:10.1038/srep39075

Cited by 78 publications

(74 citation statements)

References 40 publications

(48 reference statements)

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“…Lu et al [11] reported that the frequency of IL-4 + CD4 + T cells was increased in UC patients. Itani et al [12] found that a biased Th2 response was induced in mice with colitis. Our previous studies also found that Th2 polarization in UC patients could be alleviated by specific immunotherapy [13].…”

Section: Discussionmentioning

confidence: 99%

Survivin Impairs the Apoptotic Machinery in CD4<sup>+</sup> T Cells of Patients with Ulcerative Colitis

Feng¹,

Ma²,

Zhang³

et al. 2019

J Innate Immun

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Background: The increase in CD4 + T cell infiltration and overproduction of CD4 + T cell-associated cytokines have been observed in the inflamed colon mucosa of patients with ulcerative colitis (UC); the underlying mechanisms are not fully understood. Survivin plays a critical role in the interference with apoptotic machinery. This study aims to elucidate the role of survivin in the interference with the apoptotic machinery in CD4 + T cells of UC patients. Methods: Peripheral blood samples were collected from UC patients (UC group) and healthy subjects (healthy group). The apoptotic status in CD4 + T cells was analyzed by flow cytometry. Results: We observed that the expression of survivin was significantly higher in CD4 + T cells of UC patients than in healthy subjects. UC CD4 + T cells were resistant to apoptosis induction. A complex of survivin and c-Myc, the transcription factor of FasL, was detected in CD4 + T cells in UC patients, which prevented the binding of c-Myc to the FasL promoter and interfered with the expression of FasL. Increased expression of survivin prevented the activation-induced CD4 + T cells from apoptosis. Conclusions: The data indicate that UC CD4 + T cells express high levels of survivin, which impairs the apoptotic machinery in CD4 + T cells and prevents the activation-induced CD4 + T cell apoptosis. Therefore, target therapy against survivin has translational potential in the treatment of UC patients.

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Section: Discussionmentioning

confidence: 99%

Survivin Impairs the Apoptotic Machinery in CD4<sup>+</sup> T Cells of Patients with Ulcerative Colitis

Feng¹,

Ma²,

Zhang³

et al. 2019

J Innate Immun

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“…In China, colon cancer is the third most common cancer and ranks fifth for its mortality rate (19). The average age for a patient with colon cancer is ~40 years, with being between 50 and 60 years, 10 years less compared with the average age of Western countries (19).…”

Section: Discussionmentioning

confidence: 99%

miRNA‑29a inhibits colon cancer growth by regulation of the PTEN/Akt/GSK3β and Wnt/β‑catenin signaling pathways

et al. 2018

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Abstract. In the present study, the effects of microRNA-29a (miRNA-29a) on colon cancer cell viability and the molecular mechanisms underlying the effects were investigated. The expression of miRNA-29a in colon cancer serum samples was notably downregulated, compared with in the normal group. First, miRNA-29a mimic was used to increase the expression of miRNA-29a in HCT-116 cells. Furthermore, upregulation of miRNA-29a suppressed cell viability, increased lactate dehydrogenase levels and apoptosis, and promoted caspase-3/9 activities and B-cell lymphoma 2-associated X protein and phosphatase and tensin homolog (PTEN) protein expression in colon cancer cells. Furthermore, upregulation of miRNA-29a decreased phosphoinositide 3-kinase, phosphorylated (p)-protein kinase B (Akt) and p-glycogen synthase kinase 3β (GSK3β) protein expression and suppressed the Wnt/β-catenin signaling pathway in colon cancer cells. The results of the present study verified that the protective effects of miRNA-29a suppress the PTEN/Akt/GSK3β and Wnt/β-catenin signaling pathways in colon cancer.

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“…63,[69][70][71] As the NLRP3 inflammasome assembles in response to a vast range of DAMPs, it is likely that it senses a common cellular distress signal induced by these molecules, activation is also protective in colitis induced by another hapten, oxazolone, in a manner dependent on the production of both IL-1β and IL-18 production. 79 In contrast to these studies, other studies have reported protection from DSS or TNBS-induced colitis or AOM-DSS-induced CAC in mice deficient in the NLRP3 inflammasome components or IL-18 signaling. [80][81][82][83][84] The discrepancies in the phenotypes observed by different groups could be due to differences in microbial composition in different animal facilities, precise genetic backgrounds of the knockout mice, and experimental protocols.…”

Section: Nlrp3mentioning

confidence: 98%

“…NLRP3 also contributes to control of metastatic growth of colon cancer in the liver by promoting IL‐18‐mediated tumoricidal activity of NK cells . NLRP3 activation is also protective in colitis induced by another hapten, oxazolone, in a manner dependent on the production of both IL‐1β and IL‐18 production …”

Section: Inflammasomes In Intestinal Pathologies: Implications For Pymentioning

confidence: 99%

Inflammatory cell death in intestinal pathologies

Sharma

Kanneganti

2017

Immunological Reviews

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Summary The intestinal tract is a site of intense immune cell activity that is poised to mount an effective response against a pathogen and yet maintain tolerance towards commensal bacteria and innocuous dietary antigens. The role of cell death in gut pathologies is particularly important as the intestinal epithelium undergoes self-renewal every four to seven days through a continuous process of cell death and cell division. Cell death is also required for removal of infected, damaged and cancerous cells. Certain forms of cell death trigger inflammation through release of damage associated molecular patterns (DAMPs). Further, molecules involved in cell-death decisions also moonlight as critical nodes in immune signaling. The manner of cell death is, therefore, highly instructive of the immunological consequences that ensue. Perturbations in cell death pathways can impact the regulation of the immune system with deleterious consequences. In this review, we discuss the various forms of cell death with a special emphasis on lytic cell death pathways of pyroptosis and necroptosis and their implications in inflammation and cancer in the gut. Understanding the implications of distinct cell death pathways will help in the development of therapeutic interventions in intestinal pathologies.

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NLRP3 inflammasome has a protective effect against oxazolone-induced colitis: a possible role in ulcerative colitis

Cited by 78 publications

References 40 publications

Survivin Impairs the Apoptotic Machinery in CD4<sup>+</sup> T Cells of Patients with Ulcerative Colitis

Survivin Impairs the Apoptotic Machinery in CD4<sup>+</sup> T Cells of Patients with Ulcerative Colitis

miRNA‑29a inhibits colon cancer growth by regulation of the PTEN/Akt/GSK3β and Wnt/β‑catenin signaling pathways

Inflammatory cell death in intestinal pathologies

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