IL-36γ and IL-36Ra Reciprocally Regulate NSCLC Progression by Modulating GSH Homeostasis and Oxidative Stress-Induced Cell Death.

ABSTRACT: The balance between antioxidants and reactive oxygen species (ROS) critically regulates tumor initiation and progression. However, whether and how the tumor-favoring redox status is controlled by cytokine networks remain poorly defined. Here, it is shown that IL-36γ and IL-36Ra reciprocally regulate the progression of non-small cell lung cancer (NSCLC) by modulating glutathione metabolism and ROS resolution. Knockout, inhibition, or neutralization of IL-36γ significantly inhibits NSCLC progression and prolongs survival of the Kras^LSL-G12D/+ Tp53^fl/fl and Kras^LSL-G12D/+ Lkb1^fl/fl mice after tumor induction, whereas knockout of IL-36Ra exacerbates tumorigenesis in these NSCLC mouse models and accelerates death of mice. Mechanistically, IL-36γ direc

SUBMITTER: Wang P 

PROVIDER: S-EPMC8498882 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature