Interferon-gamma regulates inflammatory cell death by targeting necroptosis in experimental autoimmune arthritis.
Interferon-gamma regulates inflammatory cell death by targeting necroptosis in experimental autoimmune arthritis.
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DOI：
10.1038/s41598-017-09767-0
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发表时间：
2017-08-31
影响因子：
4.6
通讯作者：
Cho ML
中科院分区：
文献类型：
--
作者：
Lee SH;Kwon JY;Kim SY;Jung K;Cho ML
干扰素γ（IFN-γ）诱导炎症反应和凋亡性细胞死亡。类风湿性关节炎（RA）是一种全身性炎症性疾病，与炎症介质（包括肿瘤坏死因子α（TNF-α）和辅助性T细胞（Th）17）水平升高以及炎症细胞凋亡下调有关。我们假设IFN-γ在体外会减少炎性细胞死亡，而IFN-γ的缺失会加重体内炎症。IFN-γ下调细胞凋亡及细胞FLICE样抑制蛋白（cFLIPL）和混合谱系激酶结构域样（MLKL）的表达。然而，IFN-γ的缺失促进了cFLIPL和MLKL的产生以及坏死性凋亡。IFN-γ缺乏可增加Th17细胞数量，上调IL-17和TNF-α的表达。MLKL、受体相互作用蛋白激酶（RIPK）1和RIPK3在胶原诱导性关节炎（CIA）小鼠关节中的表达增加。与患有CIA的野生型小鼠相比，IFN-γ −/− CIA小鼠显示软骨损伤和关节炎症加重，关节中MLKL、RIPK1和RIPK3的产生加速。IFN-γ缺乏诱导信号转导和转录激活因子3的激活。这些结果表明，IFN-γ调节炎性细胞死亡，并可能在RA的治疗中使用的潜力。
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 (cFLIPL) and mixed lineage kinase domain-like (MLKL). However, loss of IFN-γ promoted the production of cFLIPL and MLKL, and necroptosis. IFN-γ deficiency increased Th17 cell number and upregulated the expression of IL-17 and TNF-α. 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-γ−/− CIA mice showed exacerbation of cartilage damage and joint inflammation, and acceleration of MLKL, RIPK1, and RIPK3 production in the joints. IFN-γ deficiency induced the activation of signal transducer and activator of transcription 3. These results suggest that IFN-γ regulates inflammatory cell death and may have potential for use in the treatment of RA.
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影响因子：
64.8
作者：
Oberst, Andrew;Dillon, Christopher P.;Weinlich, Ricardo;McCormick, Laura L.;Fitzgerald, Patrick;Pop, Cristina;Hakem, Razq;Salvesen, Guy S.;Green, Douglas R.
通讯作者：
Green, Douglas R.
影响因子：
4.6
作者：
Ranjan K;Pathak C
通讯作者：
Pathak C
细胞死亡的基本与附件方面：NCCD 2015的建议。
影响因子：
12.4
作者：
通讯作者：
--
影响因子：
32.4
作者：
Alvarez-Diaz, Silvia;Dillon, Christopher P.;Lalaoui, Najoua;Tanzer, Maria C.;Rodriguez, Diego A.;Lin, Ann;Lebois, Marion;Hakem, Razq;Josefsson, Emma C.;O'Reilly, Lorraine A.;Silke, John;Alexander, Warren S.;Green, Douglas R.;Strasser, Andreas
通讯作者：
Strasser, Andreas
影响因子：
4.9
作者：
Page CE;Smale S;Carty SM;Amos N;Lauder SN;Goodfellow RM;Richards PJ;Jones SA;Topley N;Williams AS
通讯作者：
Williams AS