Interferon-gamma regulates inflammatory cell death by targeting necroptosis in experimental autoimmune arthritis.

ABSTRACT: Interferon γ (IFN-γ) induces an inflammatory response and apoptotic cell death. Rheumatoid arthritis (RA) is a systemic inflammatory disease associated with increased levels of inflammatory mediators, including tumour necrosis factor α (TNF-α) and T helper (Th) 17 cells, and downregulation of apoptosis of inflammatory cells. We hypothesized that IFN-γ would reduce inflammatory cell death in vitro and that loss of IFN-γ would aggravate inflammation in vivo. IFN-γ downregulated necroptosis and the expression of cellular FLICE-like inhibitory protein (cFLIP_L) and mixed lineage kinase domain-like (MLKL). However, loss of IFN-γ promoted the production of cFLIP_L and MLKL, and necroptosis. IFN-γ deficiency increased Th17 cell number and upregulated the expression of IL-17 an

SUBMITTER: Lee SH 

PROVIDER: S-EPMC5579272 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature