GLCCI1 Deficiency Induces Glucocorticoid Resistance via the Competitive Binding of IRF1:GRIP1 and IRF3:GRIP1 in Asthma.

ABSTRACT: GLCCI1 plays a significant role in modulating glucocorticoid (GC) sensitivity in asthma. This project determines the underlying mechanism that GLCCI1 deficiency attenuates GC sensitivity in dexamethasone (Dex)-treated Ovalbumin (OVA)-induced asthma mice and epithelial cells through upregulating binding of IRF1:GRIP1 and IRF3:GRIP1. Dexamethasone treatment led to less reduced inflammation, airway hyperresponsiveness, and activation of the components responsible for GC activity, as determined by decreased GR and glucocorticoid receptor interacting protein 1 (GRIP1) expression but augmented IRF1 and IRF3 expression in GLCCI1^-/- asthmatic mice compared with wild type asthmatic mice. Moreover, the recruitment of GRIP1 to GR was downregulated, while the individual recruitment of GRIP1

SUBMITTER: Hu X 

PROVIDER: S-EPMC8421568 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature