title: Tumor necrosis factor and transforming growth factor β regulate clock genes by controlling the expression of the cold inducible RNA-binding protein (CIRBP).
abstract: The circadian clock drives the rhythmic expression of a broad array of genes that orchestrate metabolism, sleep wake behavior, and the immune response. Clock genes are transcriptional regulators engaged in the generation of circadian rhythms. The cold inducible RNA-binding protein (CIRBP) guarantees high amplitude expression of clock. The cytokines TNF and TGFβ impair the expression of clock genes, namely the period genes and the proline- and acidic amino acid-rich basic leucine zipper (PAR-bZip) clock-controlled genes. Here, we show that TNF and TGFβ impair the expression of Cirbp in fibroblasts and neuronal cells. IL-1β, IL-6, IFNα, and IFNγ do not exert such effects. Depletion of Cirbp is found to increase the susceptibility of cells to the TNF-mediated inhibition of high amplitude expression of clock genes and modulates the TNF-induced cytokine response. Our findings reveal a new mechanism of cytokine-regulated expression of clock genes.
authors: From the Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland.
authors: Martin
authors: M
authors: Lopez
authors: Daniel
authors: D
authors: Meier
authors: Andreas
authors: A
authors: Müller
authors: Paul
authors: P
authors: Franken
authors: Jun
authors: J
authors: Fujita
authors: Adriano
authors: A
authors: Fontana
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000276:immunology; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000235:genetics* / Q000276:immunology; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D009474:Neurons / Q000166:cytology; D020871:RNA Stability / Q000276:immunology; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D012890:Sleep / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism
chemical_list: C106176:Cirbp protein, mouse; D056925:Circadian Rhythm Signaling Peptides and Proteins; D016207:Cytokines; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha
keywords: Circadian Rhythms; Cytokine; Gene Expression; Innate Immunity; Metabolism; Sickness Behavior; Sleep