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Desmosterol: A natural product derived from macroalgae modulates inflammatory response and oxidative stress pathways in intestinal epithelial cells

The serum level of cholesterol and its biosynthetic intermediates are critical indicators to access metabolism-related disorders in humans and animals. However, the molecular actions of these intermediates on gene functions and regulation remained elusive. Here, we show that desmosterol (DES) is the...

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Autores principales: Qu, Huan, Zong, Qiufang, Hu, Ping, Li, Zhaojian, Wang, Haifei, Wu, Shenglong, Liu, Hao-Yu, Bao, Wenbin, Cai, Demin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9845693/
https://www.ncbi.nlm.nih.gov/pubmed/36685553
http://dx.doi.org/10.3389/fimmu.2022.1101643
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author Qu, Huan
Zong, Qiufang
Hu, Ping
Li, Zhaojian
Wang, Haifei
Wu, Shenglong
Liu, Hao-Yu
Bao, Wenbin
Cai, Demin
author_facet Qu, Huan
Zong, Qiufang
Hu, Ping
Li, Zhaojian
Wang, Haifei
Wu, Shenglong
Liu, Hao-Yu
Bao, Wenbin
Cai, Demin
author_sort Qu, Huan
collection PubMed
description The serum level of cholesterol and its biosynthetic intermediates are critical indicators to access metabolism-related disorders in humans and animals. However, the molecular actions of these intermediates on gene functions and regulation remained elusive. Here, we show that desmosterol (DES) is the most abundant intermediate involved in cholesterol biosynthesis and is highly enriched in red/brown algae. It exerts a pivotal role in modulating core genes involved in oxidative stress and inflammatory response processes in the ileum epithelial cells (IPI-2I). We observed that the DES extracted from red algae did not affect IPI-2I cell growth or survival. A transcriptomic measurement revealed that the genes enrolled in the oxidative process and cholesterol homeostasis pathway were significantly down-regulated by DES treatment. Consistent with this notion, cellular reactive oxygen species (ROS) levels were markedly decreased in response to DES treatment. In contrast, key inflammatory genes including IL-6, TNF-α, and IFN-γ were remarkably upregulated in the RNA-seq analysis, as further confirmed by qRT-PCR. Given that DES is a specific agonist of nuclear receptor RORγ, we also found that DES caused the elevated expression of RORγ at mRNA and protein levels, suggesting it is a potential mediator under DES administration. Together, these results underscore the vital physiological actions of DES in inflammatory and oxidative processes possibly via RORγ, and may be helpful in anti-oxidation treatment and immunotherapy in the future.
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spelling pubmed-98456932023-01-19 Desmosterol: A natural product derived from macroalgae modulates inflammatory response and oxidative stress pathways in intestinal epithelial cells Qu, Huan Zong, Qiufang Hu, Ping Li, Zhaojian Wang, Haifei Wu, Shenglong Liu, Hao-Yu Bao, Wenbin Cai, Demin Front Immunol Immunology The serum level of cholesterol and its biosynthetic intermediates are critical indicators to access metabolism-related disorders in humans and animals. However, the molecular actions of these intermediates on gene functions and regulation remained elusive. Here, we show that desmosterol (DES) is the most abundant intermediate involved in cholesterol biosynthesis and is highly enriched in red/brown algae. It exerts a pivotal role in modulating core genes involved in oxidative stress and inflammatory response processes in the ileum epithelial cells (IPI-2I). We observed that the DES extracted from red algae did not affect IPI-2I cell growth or survival. A transcriptomic measurement revealed that the genes enrolled in the oxidative process and cholesterol homeostasis pathway were significantly down-regulated by DES treatment. Consistent with this notion, cellular reactive oxygen species (ROS) levels were markedly decreased in response to DES treatment. In contrast, key inflammatory genes including IL-6, TNF-α, and IFN-γ were remarkably upregulated in the RNA-seq analysis, as further confirmed by qRT-PCR. Given that DES is a specific agonist of nuclear receptor RORγ, we also found that DES caused the elevated expression of RORγ at mRNA and protein levels, suggesting it is a potential mediator under DES administration. Together, these results underscore the vital physiological actions of DES in inflammatory and oxidative processes possibly via RORγ, and may be helpful in anti-oxidation treatment and immunotherapy in the future. Frontiers Media S.A. 2023-01-04 /pmc/articles/PMC9845693/ /pubmed/36685553 http://dx.doi.org/10.3389/fimmu.2022.1101643 Text en Copyright © 2023 Qu, Zong, Hu, Li, Wang, Wu, Liu, Bao and Cai https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Qu, Huan
Zong, Qiufang
Hu, Ping
Li, Zhaojian
Wang, Haifei
Wu, Shenglong
Liu, Hao-Yu
Bao, Wenbin
Cai, Demin
Desmosterol: A natural product derived from macroalgae modulates inflammatory response and oxidative stress pathways in intestinal epithelial cells
title Desmosterol: A natural product derived from macroalgae modulates inflammatory response and oxidative stress pathways in intestinal epithelial cells
title_full Desmosterol: A natural product derived from macroalgae modulates inflammatory response and oxidative stress pathways in intestinal epithelial cells
title_fullStr Desmosterol: A natural product derived from macroalgae modulates inflammatory response and oxidative stress pathways in intestinal epithelial cells
title_full_unstemmed Desmosterol: A natural product derived from macroalgae modulates inflammatory response and oxidative stress pathways in intestinal epithelial cells
title_short Desmosterol: A natural product derived from macroalgae modulates inflammatory response and oxidative stress pathways in intestinal epithelial cells
title_sort desmosterol: a natural product derived from macroalgae modulates inflammatory response and oxidative stress pathways in intestinal epithelial cells
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9845693/
https://www.ncbi.nlm.nih.gov/pubmed/36685553
http://dx.doi.org/10.3389/fimmu.2022.1101643
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