A new p65 isoform that bind the glucocorticoid hormone and is expressed in inflammation liver diseases and COVID-19
Abstract 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 inflam...
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Nature Portfolio
2021
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oai:doaj.org-article:0c60952f96d6426abd1c659d26d5de752021-11-28T12:18:54ZA new p65 isoform that bind the glucocorticoid hormone and is expressed in inflammation liver diseases and COVID-1910.1038/s41598-021-02119-z2045-2322https://doaj.org/article/0c60952f96d6426abd1c659d26d5de752021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02119-zhttps://doaj.org/toc/2045-2322Abstract 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.Gaetano SpinelliGiuseppa BiddeciAnna ArtaleFrancesca ValentinoGiuseppe TarantinoGiuseppe GalloFabrizio GianguzzaPier Giulio ConaldiSalvatore CorraoFrancesco GervasiTommaso Silvano AronicaAldo Di LeonardoGiovanni DuroFrancesco Di BlasiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) |
| institution |
DOAJ |
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DOAJ |
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Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Gaetano Spinelli Giuseppa Biddeci Anna Artale Francesca Valentino Giuseppe Tarantino Giuseppe Gallo Fabrizio Gianguzza Pier Giulio Conaldi Salvatore Corrao Francesco Gervasi Tommaso Silvano Aronica Aldo Di Leonardo Giovanni Duro Francesco Di Blasi A new p65 isoform that bind the glucocorticoid hormone and is expressed in inflammation liver diseases and COVID-19 |
| description |
Abstract 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. |
| format |
article |
| author |
Gaetano Spinelli Giuseppa Biddeci Anna Artale Francesca Valentino Giuseppe Tarantino Giuseppe Gallo Fabrizio Gianguzza Pier Giulio Conaldi Salvatore Corrao Francesco Gervasi Tommaso Silvano Aronica Aldo Di Leonardo Giovanni Duro Francesco Di Blasi |
| author_facet |
Gaetano Spinelli Giuseppa Biddeci Anna Artale Francesca Valentino Giuseppe Tarantino Giuseppe Gallo Fabrizio Gianguzza Pier Giulio Conaldi Salvatore Corrao Francesco Gervasi Tommaso Silvano Aronica Aldo Di Leonardo Giovanni Duro Francesco Di Blasi |
| author_sort |
Gaetano Spinelli |
| title |
A new p65 isoform that bind the glucocorticoid hormone and is expressed in inflammation liver diseases and COVID-19 |
| title_short |
A new p65 isoform that bind the glucocorticoid hormone and is expressed in inflammation liver diseases and COVID-19 |
| title_full |
A new p65 isoform that bind the glucocorticoid hormone and is expressed in inflammation liver diseases and COVID-19 |
| title_fullStr |
A new p65 isoform that bind the glucocorticoid hormone and is expressed in inflammation liver diseases and COVID-19 |
| title_full_unstemmed |
A new p65 isoform that bind the glucocorticoid hormone and is expressed in inflammation liver diseases and COVID-19 |
| title_sort |
new p65 isoform that bind the glucocorticoid hormone and is expressed in inflammation liver diseases and covid-19 |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/0c60952f96d6426abd1c659d26d5de75 |
| work_keys_str_mv |
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