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

Ting Yun Chuang, An Jie Cheng, I. Ting Chen, Tien Yun Lan, I. Hsuan Huang, Chung Wai Shiau, Chia Lin Hsu, Ya Wen Liu, Zee Fen Chang, Ping Hui Tseng, Jean Cheng Kuo*

*此作品的通信作者

研究成果: Article同行評審

21 引文 斯高帕斯(Scopus)

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.

原文English
頁(從 - 到)49735-49748
頁數14
期刊Oncotarget
8
發行號30
DOIs
出版狀態Published - 2017

指紋

深入研究「Suppression of LPS-induced inflammatory responses by the hydroxyl groups of dexamethasone」主題。共同形成了獨特的指紋。

引用此