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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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.

Original languageEnglish
Pages (from-to)49735-49748
Number of pages14
Issue number30
StatePublished - 2017


  • Dexamethasone
  • Innate immunity
  • P38 MAPK signaling
  • TNF-α secretion
  • Tumor necrosis factor-α (TNF-α)-converting enzyme


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