Article: article from journal or magazin.
Tumor necrosis factor and transforming growth factor β regulate clock genes by controlling the expression of the cold inducible RNA-binding protein (CIRBP).
Journal of Biological Chemistry
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.
Animals, Circadian Rhythm/immunology, Circadian Rhythm Signaling Peptides and Proteins/genetics, Circadian Rhythm Signaling Peptides and Proteins/immunology, Cytokines/immunology, Cytokines/metabolism, Gene Expression/immunology, Immunity, Innate/immunology, Mice, Mice, Inbred C57BL, NIH 3T3 Cells, Neurons/cytology, RNA Stability/immunology, RNA, Small Interfering/genetics, RNA-Binding Proteins/immunology, RNA-Binding Proteins/metabolism, Sleep/immunology, Transforming Growth Factor beta1/immunology, Transforming Growth Factor beta1/metabolism, Tumor Necrosis Factor-alpha/immunology, Tumor Necrosis Factor-alpha/metabolism
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