STAT3 regulates inflammatory cytokine production downstream of TNFR1 by inducing expression of TNFAIP3/A20.

ABSTRACT: Tumour Necrosis Factor (TNF) potently induces a transient inflammatory response that must be downregulated once any invasive stimulus has resolved. Yet, how TNF-induced inflammation is shut down in normal cells is incompletely understood. The present study shows that STAT3 was activated in mouse embryo fibroblasts (MEFs) by treatment with TNF or an agonist antibody to TNFR1. STAT3 activation was inhibited by pharmacological inhibition of the Jak2 tyrosine kinase that associates with TNFR1. To identify STAT3 target genes, global transcriptome analysis by RNA sequencing was performed in wild-type MEFs and MEFs from STAT3 knockout (STAT3^KO ) mice that were stimulated with TNF, and the results were validated at the protein level by using multiplex cytokine assays and immunoblotting.

SUBMITTER: Antonia RJ 

PROVIDER: S-EPMC9357623 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature