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DHEA and Its Metabolites Reduce the Cytokines Involved in the Inflammatory Response and Fibrosis in Primary Biliary Cholangitis
Dehydroepiandrosterone (DHEA) is an abundant steroid and precursor of sex hormones. During aging, the reduction in DHEA synthesis causes a significant depletion of estrogens and androgens in different organs, such as the ovaries, brain, and liver. Primary Biliary Cholangitis (PBC) is a cholestatic l...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10049419/ https://www.ncbi.nlm.nih.gov/pubmed/36982376 http://dx.doi.org/10.3390/ijms24065301 |
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author | Blatkiewicz, Małgorzata Sielatycka, Katarzyna Piotrowska, Katarzyna Kilańczyk, Ewa |
author_facet | Blatkiewicz, Małgorzata Sielatycka, Katarzyna Piotrowska, Katarzyna Kilańczyk, Ewa |
author_sort | Blatkiewicz, Małgorzata |
collection | PubMed |
description | Dehydroepiandrosterone (DHEA) is an abundant steroid and precursor of sex hormones. During aging, the reduction in DHEA synthesis causes a significant depletion of estrogens and androgens in different organs, such as the ovaries, brain, and liver. Primary Biliary Cholangitis (PBC) is a cholestatic liver disease that begins with immune-mediated bile duct damage, and is followed by liver fibrosis, and finally, cirrhosis. PBC primarily affects postmenopausal women, with an average age of diagnosis of 65 years, but younger women are also affected. Here, we analyzed the levels of DHEA, estradiol (E2), and estriol (E3) in the PBC sera of females at an age of diagnosis under 40 (n = 37) and above 65 (n = 29). Our results indicate that in PBC patients at an age of diagnosis under 40, E2 was significantly lower compared to that in healthy women. In contrast, the levels of DHEA and E3 were in a normal range. Furthermore, ELISA assays revealed that in PBC patients at an age of diagnosis above 65, the levels of DHEA, E2, and E3 significantly declined in comparison to those in younger patients. In addition, flow cytometry analysis showed that the level of IL-8 significantly decreased while the level of TNF-α increased in older PBC patients compared to younger ones. Moreover, we showed for the first time that the sulfonated form of DHEA, DHEA-S, reduces the levels of both pro-inflammatory interleukins, IL-8 and TNF-α, in PBC-like cholangiocytes (H69-miR506), while it diminishes the level of the pro-fibrotic interleukin, IL-13, in hepatocytes (Hep-G2). Finally, we demonstrated that the expression of the pro-fibrotic agent TGF-β significantly increased in both the early (F0–F3) and cirrhotic (F4) stages of PBC, and this elevation was accompanied by higher α-SMA expression. |
format | Online Article Text |
id | pubmed-10049419 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100494192023-03-29 DHEA and Its Metabolites Reduce the Cytokines Involved in the Inflammatory Response and Fibrosis in Primary Biliary Cholangitis Blatkiewicz, Małgorzata Sielatycka, Katarzyna Piotrowska, Katarzyna Kilańczyk, Ewa Int J Mol Sci Article Dehydroepiandrosterone (DHEA) is an abundant steroid and precursor of sex hormones. During aging, the reduction in DHEA synthesis causes a significant depletion of estrogens and androgens in different organs, such as the ovaries, brain, and liver. Primary Biliary Cholangitis (PBC) is a cholestatic liver disease that begins with immune-mediated bile duct damage, and is followed by liver fibrosis, and finally, cirrhosis. PBC primarily affects postmenopausal women, with an average age of diagnosis of 65 years, but younger women are also affected. Here, we analyzed the levels of DHEA, estradiol (E2), and estriol (E3) in the PBC sera of females at an age of diagnosis under 40 (n = 37) and above 65 (n = 29). Our results indicate that in PBC patients at an age of diagnosis under 40, E2 was significantly lower compared to that in healthy women. In contrast, the levels of DHEA and E3 were in a normal range. Furthermore, ELISA assays revealed that in PBC patients at an age of diagnosis above 65, the levels of DHEA, E2, and E3 significantly declined in comparison to those in younger patients. In addition, flow cytometry analysis showed that the level of IL-8 significantly decreased while the level of TNF-α increased in older PBC patients compared to younger ones. Moreover, we showed for the first time that the sulfonated form of DHEA, DHEA-S, reduces the levels of both pro-inflammatory interleukins, IL-8 and TNF-α, in PBC-like cholangiocytes (H69-miR506), while it diminishes the level of the pro-fibrotic interleukin, IL-13, in hepatocytes (Hep-G2). Finally, we demonstrated that the expression of the pro-fibrotic agent TGF-β significantly increased in both the early (F0–F3) and cirrhotic (F4) stages of PBC, and this elevation was accompanied by higher α-SMA expression. MDPI 2023-03-10 /pmc/articles/PMC10049419/ /pubmed/36982376 http://dx.doi.org/10.3390/ijms24065301 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Blatkiewicz, Małgorzata Sielatycka, Katarzyna Piotrowska, Katarzyna Kilańczyk, Ewa DHEA and Its Metabolites Reduce the Cytokines Involved in the Inflammatory Response and Fibrosis in Primary Biliary Cholangitis |
title | DHEA and Its Metabolites Reduce the Cytokines Involved in the Inflammatory Response and Fibrosis in Primary Biliary Cholangitis |
title_full | DHEA and Its Metabolites Reduce the Cytokines Involved in the Inflammatory Response and Fibrosis in Primary Biliary Cholangitis |
title_fullStr | DHEA and Its Metabolites Reduce the Cytokines Involved in the Inflammatory Response and Fibrosis in Primary Biliary Cholangitis |
title_full_unstemmed | DHEA and Its Metabolites Reduce the Cytokines Involved in the Inflammatory Response and Fibrosis in Primary Biliary Cholangitis |
title_short | DHEA and Its Metabolites Reduce the Cytokines Involved in the Inflammatory Response and Fibrosis in Primary Biliary Cholangitis |
title_sort | dhea and its metabolites reduce the cytokines involved in the inflammatory response and fibrosis in primary biliary cholangitis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10049419/ https://www.ncbi.nlm.nih.gov/pubmed/36982376 http://dx.doi.org/10.3390/ijms24065301 |
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