Klotho suppresses RIG-I-mediated senescence-associated inflammation.
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.
Mesh Terms:
Animals, Cellular Senescence, DEAD Box Protein 58, DEAD-box RNA Helicases, Endothelium, Vascular, Female, Gene Expression Regulation, Gene Silencing, Glucuronidase, Humans, Interferon Regulatory Factor-1, Interleukin-6, Interleukin-8, Klotho Proteins, Male, Mice, Phenotype, Receptors, Immunologic, Signal Transduction
Animals, Cellular Senescence, DEAD Box Protein 58, DEAD-box RNA Helicases, Endothelium, Vascular, Female, Gene Expression Regulation, Gene Silencing, Glucuronidase, Humans, Interferon Regulatory Factor-1, Interleukin-6, Interleukin-8, Klotho Proteins, Male, Mice, Phenotype, Receptors, Immunologic, Signal Transduction
Nat Cell Biol
Date: Mar. 01, 2011
PubMed ID: 21336305
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