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首页> 外文期刊>Cytokine >Functional consequences of the Asp299Gly Toll-like receptor-4 polymorphism.
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Functional consequences of the Asp299Gly Toll-like receptor-4 polymorphism.

机译：Asp299Gly Toll样受体4多态性的功能后果。

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摘要

Toll-like receptor-4 (TLR4) is a pattern-recognition receptor not only for exogenous ligands such as lipopolysaccharide (LPS) of Gram-negative bacteria, but also for endogenous ligands such as fibronectin, heat shock proteins and hyaluronan oligosaccharides. The Asp299Gly allele of the TLR4 gene has been associated with increased risk for severe infections, but reduced progression of atherosclerosis. We have investigated the consequences of the presence of Asp299Gly polymorphism after stimulation of mononuclear cells with lipopolysaccharide (LPS), the non-LPS TLR4 microbial stimuli Aspergillus fumigatus and Cryptococcus neoformans, and the endogenous TLR4 ligand heat shock protein 60. No differences in either production of the proinflammatory cytokine TNF or the antiinflammatory cytokine interleukin-10 were observed between volunteers with the wild-type allele, volunteers heterozygous for the Asp299Gly allele and one volunteer homozygous for the TLR4 variant. In conclusion, the presence of the Asp299Gly TLR4 polymorphism does not result in defective pro and antiinflammatory cytokine production after stimulation with either exogenous (LPS and non-LPS) or endogenous TLR4 ligands, and alternative explanations are likely to be responsible for the epidemiological data showing associations with inflammatory conditions. In addition, this is the first study to demonstrate that even homozygosity for the Asp299Gly mutation does not confer hyporesponsiveness to stimulation with TLR4 stimuli.
机译：Toll样受体4（TLR4）是一种模式识别受体，不仅适用于革兰氏阴性细菌的外源性配体，例如脂多糖（LPS），而且还适用于内源性的配体，例如纤连蛋白，热休克蛋白和透明质酸寡糖。 TLR4基因的Asp299Gly等位基因与严重感染的风险增加相关，但与动脉粥样硬化的进展降低有关。我们已经研究了脂多糖（LPS），非LPS TLR4微生物刺激烟曲霉和新型隐球菌以及内源性TLR4配体热激蛋白60刺激单核细胞后Asp299Gly多态性的存在的后果。在具有野生型等位基因的志愿者，对于Asp299Gly等位基因是纯合的志愿者和对于TLR4变体是一个纯合的志愿者之间，观察到促炎细胞因子TNF或抗炎细胞因子白介素10的水平。总之，Asp299Gly TLR4多态性的存在不会导致外源性（LPS和非LPS）或内源性TLR4配体刺激后的促炎和抗炎细胞因子产生缺陷，并且流行病学数据显示可能存在其他解释与炎症有关。此外，这是第一个证明即使Asp299Gly突变的纯合子也不会赋予TLR4刺激刺激低反应性的研究。

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