A new p65 isoform that bind the glucocorticoid hormone and is expressed in inflammation liver diseases and COVID-19.
Adrenal Cortex Hormones
/ metabolism
Adult
Alternative Splicing
Animals
COVID-19
/ immunology
Carcinoma, Hepatocellular
/ metabolism
Dexamethasone
/ metabolism
Female
Gene Expression
/ genetics
Gene Expression Regulation
/ genetics
Glucocorticoids
/ metabolism
Hepatitis
/ metabolism
Humans
Inflammation
/ immunology
Leukocytes, Mononuclear
/ metabolism
Liver
/ metabolism
Liver Diseases
/ immunology
Liver Neoplasms
/ metabolism
Male
Mice
Mice, Inbred C57BL
Middle Aged
NF-kappa B
/ metabolism
Protein Isoforms
Receptors, Glucocorticoid
/ immunology
SARS-CoV-2
/ pathogenicity
Transcription Factor RelA
/ immunology
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
25 11 2021
25 11 2021
Historique:
received:
24
06
2021
accepted:
09
11
2021
entrez:
26
11
2021
pubmed:
27
11
2021
medline:
15
12
2021
Statut:
epublish
Résumé
Inflammation is a physiological process whose deregulation causes some diseases including cancer. Nuclear Factor kB (NF-kB) is a family of ubiquitous and inducible transcription factors, in which the p65/p50 heterodimer is the most abundant complex, that play critical roles mainly in inflammation. Glucocorticoid Receptor (GR) is a ligand-activated transcription factor and acts as an anti-inflammatory agent and immunosuppressant. Thus, NF-kB and GR are physiological antagonists in the inflammation process. Here we show that in mice and humans there is a spliced variant of p65, named p65 iso5, which binds the corticosteroid hormone dexamethasone amplifying the effect of the glucocorticoid receptor and is expressed in the liver of patients with hepatic cirrhosis and hepatocellular carcinoma (HCC). Furthermore, we have quantified the gene expression level of p65 and p65 iso5 in the PBMC of patients affected by SARS-CoV-2 disease. The results showed that in these patients the p65 and p65 iso5 mRNA levels are higher than in healthy subjects. The ability of p65 iso5 to bind dexamethasone and the regulation of the glucocorticoid (GC) response in the opposite way of the wild type improves our knowledge and understanding of the anti-inflammatory response and identifies it as a new therapeutic target to control inflammation and related diseases.
Identifiants
pubmed: 34824310
doi: 10.1038/s41598-021-02119-z
pii: 10.1038/s41598-021-02119-z
pmc: PMC8617276
doi:
Substances chimiques
Adrenal Cortex Hormones
0
Glucocorticoids
0
NF-kappa B
0
Protein Isoforms
0
Receptors, Glucocorticoid
0
Transcription Factor RelA
0
Dexamethasone
7S5I7G3JQL
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
22913Informations de copyright
© 2021. The Author(s).
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