Opposing regulation of the late phase TNF response by mTORC1-IL-10 signaling and hypoxia in human macrophages.

ABSTRACT: Tumor necrosis factor (TNF) is best known for inducing a rapid but transient NF-κB-mediated inflammatory response. We investigated later phases of TNF signaling, after the initial transient induction of inflammatory genes has subsided, in primary human macrophages. TNF signaling induced expression of late response genes, including inhibitors of NF-κB and TLR signaling, with delayed and sustained kinetics 6-24 hr after TNF stimulation. A subset of late phase genes was expressed in rheumatoid arthritis synovial macrophages, confirming their expression under chronic inflammatory conditions in vivo. Expression of a subset of late phase genes was mediated by autocrine IL-10, which activated STAT3 with delayed kinetics. Hypoxia, which occurs at sites of infection or inflammation where TNF is exp

SUBMITTER: Huynh L 

PROVIDER: S-EPMC4997257 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature