Inflammation suppresses DLG2 expression, preventing inflammasome formation

Résumé fourni par la source

Abstract PurposeLoss of expression of DLG2 has been identified in a number of cancers to contribute to the disease by resulting in increased tumor cell proliferation and poor survival. In light of the previous evidence that DLG2 alters the cell cycle and affects proliferation, combined with indications that DLG2 is involved in NLRP3 inflammasome axis we speculated that DLG2 has an immune function. So far, there is no data that clearly elucidates this role, and this study was designed to investigate DLG2 in inflammatory colon disease and in colon cancer as well as its impact on inflammasome induction.MethodsThe DLG2 expression levels were established in publicly available inflammation, colon cancer and mouse model datasets. The overexpression and silencing of DLG2 in colon cancer cells were used to determine the effect of DLG2 expression on the activation of the inflammasome and subsequent cytokine release.ResultsDLG2 overexpression leads to a significant increase in the formation of inflammasomes with lower release of IL-6, fewer proliferating cells and fewer cells in G2/M phase. Silencing of DLG2 impaired inflammasome formation. Additionally, DLG2 overexpression increased the expression of the NF-kappa-B inhibitor NFKBIZ.ConclusionDLG2 expression is altered in response to inflammation in the gut as well as in colon cancer, resulting in altered ability to form inflammasomes and cytokine release.Trial registration: NCT03072641

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.