DEC2 Blocks the Effect of the ARNTL2/NPAS2 Dimer on the Expression of PER3 and DBP

The expression of clock genes and are disturbed in rheumatoid arthritis, an autoimmune disease with circadian variation of symptoms. We have shown that TNF is a potent inducer of these genes. We investigated the regulation of and by TNF and elucidated their effect on other clock gene expressions. Ad...

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Bibliographic Details
Published in:Journal of circadian rhythms 2017-08, Vol.15 (1), p.6-6
Main Authors: Olkkonen, Juri, Kouri, Vesa-Petteri, Kuusela, Elina, Ainola, Mari, Nordström, Dan, Eklund, Kari K, Mandelin, Jami
Format: Article
Language:English
Subjects:
Analysis
ARNTL2
Circadian
Circadian rhythms
DEC2
Development and progression
Gene expression
Genetic aspects
Inflammation
NPAS2
Physiological aspects
Rheumatoid arthritis
TNF
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Summary:The expression of clock genes and are disturbed in rheumatoid arthritis, an autoimmune disease with circadian variation of symptoms. We have shown that TNF is a potent inducer of these genes. We investigated the regulation of and by TNF and elucidated their effect on other clock gene expressions. Additionally, we studied the effect of and on and . Cultured primary human fibroblasts were stimulated with TNF and the effects on ARNTL2 and NPAS2 were studied with RT-qPCR and immunofluorescence staining. The role of NF-κB was analyzed using IKK-2 inhibitor IMD-0354. TNF promoted ARNTL2 localization into the nuclei. Similar to , the effects of TNF on and expressions were mediated via NF-κB. Cloned and were transfected into HEK293. The ARNTL2/NPAS2 dimer was a weaker inducer of and than ARNTL/NPAS2. ARNTL2 and NPAS2 are regulated by TNF via the same mechanism as DEC2. Compared to their paralogs they have unique effects on other circadian components. Our data suggest that these genes are responsible, at least in fibroblasts, for the accurate adaptation of circadian timekeeping in individual cells during inflammation.
ISSN:1740-3391
1740-3391
DOI:10.5334/jcr.149