Involvement of nuclear factor-kB and Nurr-1 in cytokine-induced transcription of proopiomelanocortin gene in AtT20 corticotroph cells

Neuroimmunomodulation
Shinobu TakayasuToshihiro Suda

Abstract

The precise mechanism whereby proinflammatory cytokines activate the hypothalamo-pituitary-adrenal axis is still unclear. We examined whether transcription factors nuclear factor (NF)-kappaB and Nurr-1 are involved in the cytokine-induced proopiomelanocortin (POMC) gene expression. The mouse corticotropinoma cell line AtT20 was treated with tumor necrosis factor-alpha (TNF-alpha) or interleukin-1beta (IL-1beta). Real-time PCR, luciferase assay and Western blotting were conducted to assess the gene expression, promoter activity and protein expression in various conditions. Intrinsic expression of NF-kappaB was confirmed by RT-PCR. An active component of NF-kappaB (p65) was upregulated in the nuclear fraction by both TNF-alpha and IL-1beta treatment in a dose- and time-related manner. These cytokines potently stimulated the promoter activity of NF-kappaB and Nurr-1. We also found rapid upregulation of the Nurr-1 gene and protein after treatment with these cytokines. Cotreatment of the cells with either of the cytokines and corticotropin-releasing hormone resulted in additive effects. Cytokine-induced Nurr-1 transcription and Nurr-1 transcription induced by overexpression of NF-kappaB were both blunted by mutagenesis within the NF...Continue Reading

Citations

Mar 12, 2011·Neuropharmacology·Dewleen G BakerDaniel T O'Connor
Dec 21, 2011·Neuropharmacology·Dong-Yih KuoShu-Chen Chu
Jan 23, 2016·Journal of Molecular Endocrinology·Jacques Drouin
Dec 27, 2018·Journal of Pineal Research·María Elisa MercauCora Beatriz Cymeryng
Jul 19, 2012·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Donatella FedeliRosita Gabbianelli
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Jan 20, 2021·Nature Communications·Divija DeshpandePeter Nawroth
Sep 12, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Ran LiTing Lei

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