| First Author | Tummala P | Year | 2021 |
| Journal | Carcinogenesis | Volume | 42 |
| Issue | 6 | Pages | 853-863 |
| PubMed ID | 33564842 | Mgi Jnum | J:306660 |
| Mgi Id | MGI:6716948 | Doi | 10.1093/carcin/bgab008 |
| Citation | Tummala P, et al. (2021) Glutathione transferase Omega 1 confers protection against azoxymethane-induced colorectal tumour formation. Carcinogenesis 42(6):853-863 |
| abstractText | 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 1beta (IL-1beta) 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-1beta and IL-18 levels as well as significantly decreased interferon (IFN)-gamma, 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-1beta 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-1beta 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. |
