2009
DOI: 10.1177/0748730409336579
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Clock Gene Modulation by TNF-α Depends on Calcium and p38 MAP Kinase Signaling

Abstract: A 24-h treatment with the cytokine tumor necrosis factor-alpha (TNF-alpha) suppresses transcription of E-box-driven clock genes (D-site albumin promoter binding protein, Dbp; Tyrotroph embryonic factor, Tef ; Hepatic leukemia factor, Hlf; Period homolog to Drosophila 1/2/3, Per1, Per2, and Per3) by yet unknown molecular mechanisms. The attenuation of clock genes has been suggested as a putative cause for the development of sickness behavior syndrome in infectious and autoimmune diseases. Here, the authors stud… Show more

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Cited by 82 publications
(58 citation statements)
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“…Moreover, TNF inhibited the expression of E-box reporter constructs of the Dbp gene that was co-transfected with plasmids expressing CLOCK and BMAL1 proteins; the expression of mutated E-box reporter constructs was not altered by TNF (17). Studies using fibroblasts with a deletion of either Per1 and Per2 or Cry1 and Cry2 ruled out the possibility that TNF activates the repressor loop mediated by PER-CRY complexes (31).…”
Section: Discussionmentioning
confidence: 99%
“…Moreover, TNF inhibited the expression of E-box reporter constructs of the Dbp gene that was co-transfected with plasmids expressing CLOCK and BMAL1 proteins; the expression of mutated E-box reporter constructs was not altered by TNF (17). Studies using fibroblasts with a deletion of either Per1 and Per2 or Cry1 and Cry2 ruled out the possibility that TNF activates the repressor loop mediated by PER-CRY complexes (31).…”
Section: Discussionmentioning
confidence: 99%
“…Besides effects of the circadian system on the immune response, the immune system also influences the circadian clock. TNF inhibits the expression of all three Period genes, of Cry-1 and -2 and of the PAR-bZip transcription factors Dbp, Tef and Hlf (Cavadini et al, 2007;Petrzilka et al, 2009). At least some of these effects are due to an interference with E-box-dependent transcription (Cavadini et al, 2007).…”
Section: Abnormal Clock Gene System In Autoimmune Diseases and Depresmentioning
confidence: 99%
“…Furthermore, Bmal1 appears to regulate the development of B-cells [97] and in macrophages a circadian clock controls inflammatory immune responses [98]. Interestingly, IFN-c affects electrical activity and clock gene expression in SCN neurons [99] and tumor necrosis factor alpha (TNF-alpha) suppresses expression of clock genes by interfering with E-box mediated transcription [100] depending on calcium and p38 MAP kinase signaling [101]. These findings indicate a feedback regulation between the circadian and the immune system.…”
Section: The Impact Of Clock Genes On Physiologymentioning
confidence: 99%