Klotho suppresses RIG-I-mediated senescence-associated inflammation
Klotho suppresses RIG-I-mediated senescence-associated inflammation
复制标题
DOI：
10.1038/ncb2167
复制
发表时间：
2011-03-01
影响因子：
21.3
通讯作者：
Gu, Jun
中科院分区：
文献类型：
--
作者：
Liu, Feng;Wu, Su;Gu, Jun
众所周知，老化或衰老细胞发展出复杂的衰老相关分泌表型（SASP），这在培养物和体内都可以观察到。然而，诱导SASP的潜在机制在很大程度上是未知的。我们证明，视黄酸诱导基因-I（RIG-I）诱导通过共济失调毛细血管扩张突变的干扰素调节因子1（ATM-IRF 1）轴在衰老细胞和RIG-I信号介导的两个重要的炎症介质，白细胞介素-6（IL-6）和IL-8的表达。Klotho与衰老有关。我们在这里表明，细胞内，但不是分泌，形式的klotho与RIG-I相互作用，这种相互作用抑制RIG-I诱导的IL-6和IL-8的表达在体外和体内。我们的研究揭示了klotho通过抑制RIG-I介导的炎症作为抗衰老因子发挥作用的机制。
It is well known that aged or senescent cells develop a complex senescence-associated secretory phenotype (SASP), which is observed both in culture and in vivo. However, the mechanisms underlying the induction of the SASP are largely unknown. We demonstrate that retinoic-acid-inducible gene-I (RIG-I) is induced through the ataxia telangiectasia mutated-interferon regulatory factor 1 (ATM-IRF1) axis in senescent cells and that RIG-I signalling mediates the expression of two important mediators of inflammation, interleukin-6 (IL-6) and IL-8. Klotho has been associated with ageing. We show here that the intracellular, but not the secreted, form of klotho interacts with RIG-I and that this interaction inhibits RIG-I-induced expression of IL-6 and IL-8 both in vitro and in vivo. Our study uncovers a mechanism in which klotho functions as an anti-ageing factor through the suppression of RIG-I-mediated inflammation.