| First Author | Lee SH | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 10133 |
| PubMed ID | 28860618 | Mgi Jnum | J:256341 |
| Mgi Id | MGI:6108804 | Doi | 10.1038/s41598-017-09767-0 |
| Citation | Lee SH, et al. (2017) Interferon-gamma regulates inflammatory cell death by targeting necroptosis in experimental autoimmune arthritis. Sci Rep 7(1):10133 |
| abstractText | Interferon gamma (IFN-gamma) 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 alpha (TNF-alpha) and T helper (Th) 17 cells, and downregulation of apoptosis of inflammatory cells. We hypothesized that IFN-gamma would reduce inflammatory cell death in vitro and that loss of IFN-gamma would aggravate inflammation in vivo. IFN-gamma downregulated necroptosis and the expression of cellular FLICE-like inhibitory protein (cFLIPL) and mixed lineage kinase domain-like (MLKL). However, loss of IFN-gamma promoted the production of cFLIPL and MLKL, and necroptosis. IFN-gamma deficiency increased Th17 cell number and upregulated the expression of IL-17 and TNF-alpha. Expression of MLKL, receptor interacting protein kinase (RIPK)1, and RIPK3 was increased in the joints of mice with collagen-induced arthritis (CIA). Compared with wild-type mice with CIA, IFN-gamma(-/-) CIA mice showed exacerbation of cartilage damage and joint inflammation, and acceleration of MLKL, RIPK1, and RIPK3 production in the joints. IFN-gamma deficiency induced the activation of signal transducer and activator of transcription 3. These results suggest that IFN-gamma regulates inflammatory cell death and may have potential for use in the treatment of RA. |
