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Suppression of LPS-induced inflammatory responses by the hydroxyl groups of dexamethasone

The innate immune response is a central process that is activated during pathogenic infection in order to maintain physiological homeostasis. It is well known that dexamethasone (Dex), a synthetic glucocorticoid, is a potent immunosuppressant that inhibits the cytokine production induced by bacteria...

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Autores principales: Chuang, Ting-Yun, Cheng, An-Jie, Chen, I-Ting, Lan, Tien-Yun, Huang, I-Hsuan, Shiau, Chung-Wai, Hsu, Chia-Lin, Liu, Ya-Wen, Chang, Zee-Fen, Tseng, Ping-Hui, Kuo, Jean-Cheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564803/
https://www.ncbi.nlm.nih.gov/pubmed/28537905
http://dx.doi.org/10.18632/oncotarget.17683
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author Chuang, Ting-Yun
Cheng, An-Jie
Chen, I-Ting
Lan, Tien-Yun
Huang, I-Hsuan
Shiau, Chung-Wai
Hsu, Chia-Lin
Liu, Ya-Wen
Chang, Zee-Fen
Tseng, Ping-Hui
Kuo, Jean-Cheng
author_facet Chuang, Ting-Yun
Cheng, An-Jie
Chen, I-Ting
Lan, Tien-Yun
Huang, I-Hsuan
Shiau, Chung-Wai
Hsu, Chia-Lin
Liu, Ya-Wen
Chang, Zee-Fen
Tseng, Ping-Hui
Kuo, Jean-Cheng
author_sort Chuang, Ting-Yun
collection PubMed
description The innate immune response is a central process that is activated during pathogenic infection in order to maintain physiological homeostasis. It is well known that dexamethasone (Dex), a synthetic glucocorticoid, is a potent immunosuppressant that inhibits the cytokine production induced by bacterial lipopolysaccharides (LPS). Nevertheless, the extent to which the functional groups of Dex control the excessive activation of inflammatory reactions remains unknown. Furthermore, importantly, the role of Dex in the innate immune response remains unclear. Here we explore the mechanism of LPS-induced TNF-α secretion and reveal p38 MAPK signaling as a target of Dex that is involved in control of tumor necrosis factor-α (TNF-α)-converting enzyme (TACE) activity; that later mediates the shedding of TNF-α that allows its secretion. We further demonstrate that the 11-hydroxyl and 21-hydroxyl groups of Dex are the main groups that are involved in reducing LPS-induced TNF-α secretion by activated macrophages. Blockage of the hydroxyl groups of Dex inhibits immunosuppressant effect of Dex during LPS-induced TNF-α secretion and mouse mortality. Our findings demonstrate Dex signaling is involved in the control of innate immunity.
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spelling pubmed-55648032017-08-23 Suppression of LPS-induced inflammatory responses by the hydroxyl groups of dexamethasone Chuang, Ting-Yun Cheng, An-Jie Chen, I-Ting Lan, Tien-Yun Huang, I-Hsuan Shiau, Chung-Wai Hsu, Chia-Lin Liu, Ya-Wen Chang, Zee-Fen Tseng, Ping-Hui Kuo, Jean-Cheng Oncotarget Research Paper The innate immune response is a central process that is activated during pathogenic infection in order to maintain physiological homeostasis. It is well known that dexamethasone (Dex), a synthetic glucocorticoid, is a potent immunosuppressant that inhibits the cytokine production induced by bacterial lipopolysaccharides (LPS). Nevertheless, the extent to which the functional groups of Dex control the excessive activation of inflammatory reactions remains unknown. Furthermore, importantly, the role of Dex in the innate immune response remains unclear. Here we explore the mechanism of LPS-induced TNF-α secretion and reveal p38 MAPK signaling as a target of Dex that is involved in control of tumor necrosis factor-α (TNF-α)-converting enzyme (TACE) activity; that later mediates the shedding of TNF-α that allows its secretion. We further demonstrate that the 11-hydroxyl and 21-hydroxyl groups of Dex are the main groups that are involved in reducing LPS-induced TNF-α secretion by activated macrophages. Blockage of the hydroxyl groups of Dex inhibits immunosuppressant effect of Dex during LPS-induced TNF-α secretion and mouse mortality. Our findings demonstrate Dex signaling is involved in the control of innate immunity. Impact Journals LLC 2017-05-08 /pmc/articles/PMC5564803/ /pubmed/28537905 http://dx.doi.org/10.18632/oncotarget.17683 Text en Copyright: © 2017 Chuang et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Chuang, Ting-Yun
Cheng, An-Jie
Chen, I-Ting
Lan, Tien-Yun
Huang, I-Hsuan
Shiau, Chung-Wai
Hsu, Chia-Lin
Liu, Ya-Wen
Chang, Zee-Fen
Tseng, Ping-Hui
Kuo, Jean-Cheng
Suppression of LPS-induced inflammatory responses by the hydroxyl groups of dexamethasone
title Suppression of LPS-induced inflammatory responses by the hydroxyl groups of dexamethasone
title_full Suppression of LPS-induced inflammatory responses by the hydroxyl groups of dexamethasone
title_fullStr Suppression of LPS-induced inflammatory responses by the hydroxyl groups of dexamethasone
title_full_unstemmed Suppression of LPS-induced inflammatory responses by the hydroxyl groups of dexamethasone
title_short Suppression of LPS-induced inflammatory responses by the hydroxyl groups of dexamethasone
title_sort suppression of lps-induced inflammatory responses by the hydroxyl groups of dexamethasone
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564803/
https://www.ncbi.nlm.nih.gov/pubmed/28537905
http://dx.doi.org/10.18632/oncotarget.17683
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