1α,25-Dihydroxyvitamin D3 upregulates HIF-1 and TREM-1 via mTOR signaling

Bitnara Lee, Eunji Kwon, Yongjin Kim, Jin Hee Kim, Sang Wook Son, Jin Kyu Lee, Dong Won Kim, Jeongwon Sohn, Tae Hwan Kim, Jong Dae Ji

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Triggering receptor expressed on myeloid cells-1 (TREM-1) is induced by 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) in human monocytes/macrophages and epithelial cells. However, little information is available regarding the mechanism of 1,25(OH)2D3-induced TREM-1 expression in human monocytes/macrophages. In this study, 1,25(OH)2D3 was shown to strongly upregulate hypoxia-inducible transcription factor (HIF) in PMA-differentiated U937 cells. However, HIF was not mainly involved in 1,25(OH)2D3-induced TREM-1 expression. Instead, 1,25(OH)2D3-induced expression of TREM-1 was inhibited by rapamycin, a specific inhibitor of the mammalian target of rapamycin (mTOR) signaling pathway, indicating the involvement of mTOR. Induction of HIF proteins by 1,25(OH)2D3 was also inhibited by rapamycin. In addition, 1,25(OH)2D3 induced the phosphorylation of p70S6 kinase, a target of mTOR complex 1 (mTORC1). Our results suggest that 1,25(OH)2D3 induces the expression of TREM-1 through the mTOR signaling pathway in human macrophages.

Original languageEnglish
Pages (from-to)14-21
Number of pages8
JournalImmunology Letters
Volume163
Issue number1
DOIs
Publication statusPublished - 2015 Jan 1

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Keywords

  • 1α,25-dihydroxyviamin D
  • Macrophages
  • Monocytes
  • MTOR
  • TREM-1

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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