Tumor necrosis factor and transforming growth factor beta regulate clock genes by controlling the expression of the cold inducible RNA – binding protein (CIRBP).
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.
Circadian rhythms, Cytokine, Gene expression, Innate immunity, Metabolism, sickness behavior, sleep
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