Hormonal Regulation of the MHC Class I Gene in Thyroid Cells: Role of the Promoter "Tissue-Specific" Region.
Animals
Antithyroid Agents
/ pharmacology
Cell Line
Electrophoretic Mobility Shift Assay
Gene Expression Regulation
/ drug effects
Genes, MHC Class I
/ drug effects
Glucose
/ pharmacology
Hormones
/ physiology
Methimazole
/ analogs & derivatives
Rats
Thiones
/ pharmacology
Thymosin
/ pharmacology
Thyroid Gland
/ cytology
Thyroiditis, Autoimmune
/ genetics
Thyrotropin
/ pharmacology
Transcription Factors
/ genetics
AP-1
NF-kB
c-jun
hormonal regulation
major histocompatibility complex class I (MHC-1)
p65
thyroid
Journal
Frontiers in endocrinology
ISSN: 1664-2392
Titre abrégé: Front Endocrinol (Lausanne)
Pays: Switzerland
ID NLM: 101555782
Informations de publication
Date de publication:
2021
2021
Historique:
received:
29
07
2021
accepted:
15
11
2021
entrez:
23
12
2021
pubmed:
24
12
2021
medline:
11
2
2022
Statut:
epublish
Résumé
In previous studies we have demonstrated that the expression of the Major Histocompatibility Complex (MHC) class I gene in thyrocytes is controlled by several hormones, growth factors, and drugs. These substances mainly act on two regions of the MHC class I promoter a "tissue-specific" region (-800 to -676 bp) and a "hormone/cytokines-sensitive" region (-500 to -68 bp). In a previous study, we have shown that the role of the "tissue-specific" region in the MHC class I gene expression is dominant compared to that of the "hormone/cytokines-sensitive" region. In the present report we further investigate the dominant role of the "tissue-specific" region evaluating the effect of thyroid stimulating hormone (TSH), methimazole (MMI), phenylmethimazole (C10), glucose and thymosin-α1. By performing experiments of electrophoretic mobility shift assays (EMSAs) we show that TSH, MMI and C10, which inhibit MHC class I expression, act on the "tissue-specific" region increasing the formation of a silencer complex. Glucose and thymosin-α1, which stimulate MHC class I expression, act decreasing the formation of this complex. We further show that the silencer complex is formed by two distinct members of the transcription factors families activator protein-1 (AP-1) and nuclear factor-kB (NF-kB), c-jun and p65, respectively. These observations are important in order to understand the regulation of MHC class I gene expression in thyroid cells and its involvement in the development of thyroid autoimmunity.
Identifiants
pubmed: 34938270
doi: 10.3389/fendo.2021.749609
pmc: PMC8685237
doi:
Substances chimiques
Antithyroid Agents
0
Hormones
0
Thiones
0
Transcription Factors
0
phenyl methimazole
0
Methimazole
554Z48XN5E
Thymosin
61512-21-8
Thyrotropin
9002-71-5
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
749609Informations de copyright
Copyright © 2021 Giuliani, Verrocchio, Verginelli, Bucci, Grassadonia and Napolitano.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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