Uric acid as a danger signal in gout and its comorbidities.
Uric acid as a danger signal in gout and its comorbidities.
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DOI：
10.1038/nrrheum.2012.143
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发表时间：
2013-01
期刊：
影响因子：
--
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中科院分区：
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尿酸是嘌呤分解代谢的废物。当这种分子在关节或其他组织中成核形成尿酸钠 (MSU) 晶体并从而引起痛风炎症时，它引起了临床关注。痛风患者还经常患有多种并发症，包括高血压、糖尿病和心血管疾病。为什么 MSU 晶体会引发炎症并与痛风合并症相关，但最近的研究为这些问题提供了新的见解。尿酸不仅仅是一种废物，它还可以发挥病理生理学作用，作为局部警报信号，提醒免疫系统注意细胞损伤，并有助于触发先天性和适应性免疫反应。当尿酸盐晶体触发炎症小体依赖性和独立途径产生促炎细胞因子 IL-1 时，就会引起这些免疫反应的炎症成分。由此产生的生物活性 IL-1 会刺激痛风炎症，并可能导致其他合并症的发生。令人惊讶的是，对许多刺激性颗粒的炎症反应也存在相同的机制，其中许多刺激性颗粒也会引起疾病。这些新见解有助于解释痛风的发病机制，并为痛风和其他无菌性炎症性疾病指出潜在的新治疗靶点。
Uric acid is a waste product of purine catabolism. This molecule comes to clinical attention when it nucleates to form crystals of monosodium urate (MSU) in joints or other tissues and thereby causes the inflammatory disease of gout. Patients with gout also frequently suffer from a number of co-morbid conditions including hypertension, diabetes mellitus and cardiovascular disease. Why MSU crystals trigger inflammation and are associated with comorbidities of gout has been unclear, but recent studies provide new insights these issues. Rather than simply being a waste product, uric acid could serve a pathophysiological role as a local alarm signal that alerts the immune system to cell injury and helps to trigger both innate and adaptive immune responses. The inflammatory component of these immune responses is caused when urate crystals trigger both inflammasome-dependent and independent pathways to generate the proinflammatory cytokine IL-1. The resulting bioactive IL-1 stimulates the inflammation of gout and might contribute to the development of other comorbidities. Surprisingly, the same mechanisms underlie the inflammatory response to a number of irritant particles, many of which also cause disease. These new insights help to explain the pathogenesis of gout and point to potential new therapeutic targets for this and other sterile inflammatory diseases.
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影响因子：
16
作者：
Afonina IS;Tynan GA;Logue SE;Cullen SP;Bots M;Lüthi AU;Reeves EP;McElvaney NG;Medema JP;Lavelle EC;Martin SJ
通讯作者：
Martin SJ
DOI：
10.1073/pnas.78.11.6858
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
AMES, BN;CATHCART, R;HOCHSTEIN, P
通讯作者：
HOCHSTEIN, P
影响因子：
56.9
作者：
Dostert, Catherine;Petrilli, Virginie;Tschopp, Jurg
通讯作者：
Tschopp, Jurg
DOI：
10.4049/jimmunol.0901363
发表时间：
2009-07-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bauernfeind FG;Horvath G;Stutz A;Alnemri ES;MacDonald K;Speert D;Fernandes-Alnemri T;Wu J;Monks BG;Fitzgerald KA;Hornung V;Latz E
通讯作者：
Latz E
影响因子：
37.8
作者：
Farquharson, CA;Butler, R;Struthers, AD
通讯作者：
Struthers, AD