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首页> 外文期刊>Cellular immunology >Adenosine A(2A) receptor activation limits chronic granulomatous disease-induced hyperinflammation.
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Adenosine A(2A) receptor activation limits chronic granulomatous disease-induced hyperinflammation.

机译:腺苷A(2A)受体激活限制慢性肉芽肿疾病诱导的高炎症。

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摘要

Chronic granulomatous disease (CGD) is caused by defects in the NADPH oxidase complex and is characterized by an increased susceptibility to infection. Other significant complications of CGD include autoimmunity and non-infectious hyperinflammatory disorders. We show that a gp91(phox) deficiency leads to the development of phenotypically altered T lymphocytes in mice and that this abnormal, hyperactive phenotype can be modulated by activation of the adenosine A(2A) receptor. T cells isolated from CGD mice produce significantly higher levels of the pro-inflammatory cytokines IFN-gamma, IL-2, TNF-alpha, IL-4 and IL-13 than do WT cells after TCR-mediated activation; treatment with the selective adenosine A(2A) receptor agonist, CGS21680, potently inhibits this response. Additionally, the over exuberant inflammatory response elicited by thioglycollate challenge in gp91(phox) deficient mice is attenuated by CGS21680. These data suggest that treatment with A(2A)R agonists may be an effective therapy by which to regulate the immune system hyperactivity that results from a gp91(phox) deficiency.
机译:慢性肉芽肿疾病(CGD)是由NADPH氧化酶复合物中的缺陷引起的,其特征在于对感染的易感性增加。 CGD的其他显着并发症包括自身免疫和非传染性高炎症疾病。我们表明GP91(PHOX)缺乏导致小鼠中表型改变的T淋巴细胞的发展,并且通过激活腺苷A(2A)受体可以调节这种异常,过活性表型。从CGD小鼠中分离的T细胞产生比TCR介导的活化后的WT细胞产生显着更高的促炎细胞因子IFN-γ,IL-2,TNF-α,IL-4和IL-13;用选择性腺苷A(2a)受体激动剂CGS21680的处理效果抑制了这种反应。另外,通过CGS21680衰减通过GP91(PHOX)缺陷小鼠的噻golycollat​​e攻击引发的过繁殖的炎症反应。这些数据表明,用(2A)r激动剂的治疗可能是有效的治疗,由此调节来自GP91(PHOX)缺乏的免疫系统多动。

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