https://scholars.lib.ntu.edu.tw/handle/123456789/416759
標題: | Suppression of LPS-induced inflammatory responses by the hydroxyl groups of dexamethasone | 作者: | Chuang, Ting-Yun Cheng, An-Jie Chen, I-Ting Lan, Tien-Yun Huang, I-Hsuan Shiau, Chung-Wai CHIA-LIN HSU YA-WEN LIU ZEE-FEN CHANG Tseng, Ping-Hui Kuo, Jean-Cheng |
關鍵字: | TNF-α secretion; dexamethasone; innate immunity; p38 MAPK signaling; tumor necrosis factor-α (TNF-α)-converting enzyme | 公開日期: | 25-七月-2017 | 出版社: | IMPACT JOURNALS LLC | 卷: | 8 | 期: | 30 | 起(迄)頁: | 49735 | 來源出版物: | Oncotarget | 摘要: | 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. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85025824234&doi=10.18632%2foncotarget.17683&partnerID=40&md5=d5339dacf322a0adfe960758c42bbfc5 https://scholars.lib.ntu.edu.tw/handle/123456789/416759 |
ISSN: | 1949-2553 | DOI: | 10.18632/oncotarget.17683 |
顯示於: | 分子醫學研究所 |
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