Glutathione transferase Omega 1 confers protection against azoxymethane-induced colorectal tumour formation
| العنوان: | Glutathione transferase Omega 1 confers protection against azoxymethane-induced colorectal tumour formation |
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| المؤلفون: | Mark M. Hughes, Nilisha Fernando, Shuhei Takahashi, Padmaja Tummala, Melissa Rooke, Marco G. Casarotto, Jane E. Dahlstrom, Philip G. Board, Luke A. J. O'Neill |
| المصدر: | Carcinogenesis. 42:853-863 |
| بيانات النشر: | Oxford University Press (OUP), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Colorectal cancer, medicine.medical_treatment, Interleukin-1beta, Azoxymethane, Inflammatory bowel disease, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Animals, Colitis, Glutathione Transferase, Inflammation, Mice, Knockout, biology, business.industry, Dextran Sulfate, Interleukin-18, Inflammasome, General Medicine, medicine.disease, digestive system diseases, 3. Good health, Mice, Inbred C57BL, 030104 developmental biology, Cytokine, Glutathione S-transferase, chemistry, 030220 oncology & carcinogenesis, Carcinogens, Cancer research, biology.protein, Interleukin 18, Carrier Proteins, Colorectal Neoplasms, business, medicine.drug |
| الوصف: | Inflammatory bowel disease (IBD) is characterized by multiple alterations in cytokine expression and is a risk factor for colon cancer. The Omega class glutathione transferase GSTO1-1 regulates the release of the pro-inflammatory cytokines interleukin 1β (IL-1β) and interleukin 18 (IL-18) by deglutathionylating NEK7 in the NLRP3 inflammasome. When treated with azoxymethane and dextran sodium sulphate (AOM/DSS) as a model of IBD, Gsto1−/− mice were highly sensitive to colitis and showed a significant increase in the size and number of colon tumours compared with wild-type (WT) mice. Gsto1−/− mice treated with AOM/DSS had significantly lower serum IL-1β and IL-18 levels as well as significantly decreased interferon (IFN)-γ, decreased pSTAT1 and increased pSTAT3 levels in the distal colon compared with similarly treated WT mice. Histologically, AOM/DSS treated Gsto1−/− mice showed increased active chronic inflammation with macrophage infiltration, epithelial dysplasia and invasive adenocarcinoma compared with AOM/DSS treated WT mice. Thus, this study shows that GSTO1-1 regulates IL-1β and IL-18 activation and protects against colorectal cancer formation in the AOM/DSS model of IBD. The data suggest that while GSTO1-1 is a new target for the regulation of the NLRP3 inflammasome-associated cytokines IL-1β and IL-18 by small molecule inhibitors, there is a possibility that anti-inflammatory drugs targeting these cytokines may potentiate colon cancer in some situations. |
| تدمد: | 1460-2180 0143-3334 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::55294745611df6eef10f8a449c9f3e17 https://doi.org/10.1093/carcin/bgab008 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....55294745611df6eef10f8a449c9f3e17 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602180 01433334 |
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