The role of the circadian clock in rheumatoid arthritis.
The role of the circadian clock in rheumatoid arthritis.
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DOI：
10.1186/ar4146
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发表时间：
2013-02-21
影响因子：
4.9
通讯作者：
Ray DW
中科院分区：
文献类型：
--
作者：
Gibbs JE;Ray DW
风湿性关节炎表现出症状的昼夜变化，患者在清晨遭受疼痛增加的关节僵硬。这与促炎细胞因子（如白细胞介素-6）的循环水平在清晨升高有关。疾病病理学中的这种时间变化由昼夜节律钟指导，在系统水平上，通过源自中央时钟的信号传导途径，在局部水平上，通过在炎症器官和细胞内发现的自主时钟。事实上，参与类风湿性关节炎发病机制的免疫系统的许多细胞组分具有促进其功能的时间门控的独立时钟。此外，生物钟调节几种基因和蛋白质的表达和活性，这些基因和蛋白质在这种自身免疫性疾病的进展中发挥作用。这些包括许多核受体和脂肪衍生的脂肪因子。利用我们所掌握的关于生物钟如何调节炎症反应的知识，将有助于开发时间疗法方案，以提高当前治疗策略的疗效。此外，对生物钟与免疫系统耦合的机制的充分理解可能为治疗这种使人衰弱的疾病提供新的治疗靶点。
Rheumatoid arthritis exhibits diurnal variation in symptoms, with patients suffering with increased painful joint stiffness in the early morning. This correlates with an early morning rise in circulating levels of pro-inflammatory cytokines, such as interleukin-6. This temporal variation in disease pathology is directed by the circadian clock, both at a systemic level, through signalling pathways derived in the central clock, and at a local level by autonomous clocks found within inflammatory organs and cells. Indeed, many cellular components of the immune system, which are involved in the pathogenesis of rheumatoid arthritis, possess independent clocks that facilitate temporal gating of their functions. Furthermore, the circadian clock regulates the expression and activity of several genes and proteins that have demonstrated roles in progression of this autoimmune disease. These include a number of nuclear receptors and also fat-derived adipokines. Employing the knowledge we have about how the inflammatory response is regulated by the clock will facilitate the development of chronotherapy regimens to improve the efficacy of current treatment strategies. Furthermore, a full understanding of the mechanisms by which the clock couples to the immune system may provide novel therapeutic targets for the treatment of this debilitating disease.
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影响因子：
27.4
作者：
Buttgereit F;Mehta D;Kirwan J;Szechinski J;Boers M;Alten RE;Supronik J;Szombati I;Romer U;Witte S;Saag KG
通讯作者：
Saag KG
影响因子：
3.7
作者：
Charmandari, Evangelia;Chrousos, George P.;Kino, Tomoshige
通讯作者：
Kino, Tomoshige
DOI：
10.1073/pnas.1106750109
发表时间：
2012-01-10
影响因子：
11.1
作者：
Gibbs, Julie E.;Blaikley, John;Loudon, Andrew S. I.
通讯作者：
Loudon, Andrew S. I.
影响因子：
27.4
作者：
Arvidson, NG;Gudbjornsson, B;Hallgren, R
通讯作者：
Hallgren, R
影响因子：
29
作者：
Grimaldi B;Bellet MM;Katada S;Astarita G;Hirayama J;Amin RH;Granneman JG;Piomelli D;Leff T;Sassone-Corsi P
通讯作者：
Sassone-Corsi P