首页> 外文期刊>Cellular immunology >Differential cytokine secretion results from p65 and c-Rel NF-kappaB subunit signaling in peripheral blood mononuclear cells of TNF receptor-associated periodic syndrome patients.
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Differential cytokine secretion results from p65 and c-Rel NF-kappaB subunit signaling in peripheral blood mononuclear cells of TNF receptor-associated periodic syndrome patients.

机译:TNF受体相关的周期性综合征患者外周血单个核细胞中p65和c-Rel NF-kappaB亚基信号传导导致细胞因子分泌差异。

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摘要

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal dominant autoinflammatory condition caused by mutations in the TNFRSF1A gene which encodes the tumor necrosis factor (TNF) receptor, TNFR1. We investigated the effect of three high penetrance and three low penetrance TNFRSF1A mutations upon NF-kappaB transcription factor family subunit activity, and the resulting impact upon secretion of 25 different cytokines. Whilst certain mutations resulted in elevated NF-kappaB p65 subunit activity, others instead resulted in elevated c-Rel subunit activity. Interestingly, high p65 activity was associated with elevated IL-8 secretion, whereas high c-Rel activity increased IL-1beta and IL-12 secretion. In conclusion, while all six TNFRSF1A mutations showed enhanced NF-kappaB activity, different mutations stimulated distinct NF-kappaB family subunit activities, and this in turn resulted in the generation of unique cytokine secretory profiles.
机译:肿瘤坏死因子受体相关的周期性综合征(TRAPS)是一种常染色体显性遗传性自体炎症,是由编码肿瘤坏死因子(TNF)受体TNFR1的TNFRSF1A基因突变引起的。我们调查了三个高渗透率和三个低渗透率TNFRSF1A突变对NF-κB转录因子家族亚基活性的影响,以及对25种不同细胞因子分泌的影响。虽然某些突变导致NF-κBp65亚基活性升高,但其他突变却导致c-Rel亚基活性升高。有趣的是,高p65活性与升高的IL-8分泌有关,而高c-Rel活性则增加了IL-1beta和IL-12分泌。总之,尽管所有六个TNFRSF1A突变均显示出增强的NF-kappaB活性,但不同的突变刺激了不同的NF-kappaB家族亚基活性,这反过来又导致了独特的细胞因子分泌谱的产生。

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