Glutathione transferase Omega 1 confers protection against azoxymethane-induced colorectal tumour formation
| Autor: | 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 |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
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 |
| Zdroj: | Carcinogenesis. 42:853-863 |
| ISSN: | 1460-2180 0143-3334 |
| DOI: | 10.1093/carcin/bgab008 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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