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

doi:10.1016/j.imlet.2014.11.004

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

Department of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

11 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 language	English
Pages (from-to)	14-21
Number of pages	8
Journal	Immunology Letters
Volume	163
Issue number	1
DOIs	https://doi.org/10.1016/j.imlet.2014.11.004
Publication status	Published - 2015 Jan 1

Bibliographical note

Funding Information:
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2013R1A1A2001950 ).

Publisher Copyright:
© 2014 Elsevier B.V.

Keywords

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

ASJC Scopus subject areas

Immunology and Allergy
Immunology

Access to Document

10.1016/j.imlet.2014.11.004

Cite this

@article{bd26628e354d451985bac33cc0c20966,

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

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.",

keywords = "1α,25-dihydroxyviamin D, MTOR, Macrophages, Monocytes, TREM-1",

author = "Bitnara Lee and Eunji Kwon and Yongjin Kim and Kim, {Jin Hee} and Son, {Sang Wook} and Lee, {Jin Kyu} and Kim, {Dong Won} and Jeongwon Sohn and Kim, {Tae Hwan} and Ji, {Jong Dae}",

note = "Funding Information: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2013R1A1A2001950 ). Publisher Copyright: {\textcopyright} 2014 Elsevier B.V.",

year = "2015",

month = jan,

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doi = "10.1016/j.imlet.2014.11.004",

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T1 - 1α,25-Dihydroxyvitamin D3 upregulates HIF-1 and TREM-1 via mTOR signaling

AU - Lee, Bitnara

AU - Kwon, Eunji

AU - Kim, Yongjin

AU - Kim, Jin Hee

AU - Son, Sang Wook

AU - Lee, Jin Kyu

AU - Kim, Dong Won

AU - Sohn, Jeongwon

AU - Kim, Tae Hwan

AU - Ji, Jong Dae

N1 - Funding Information: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2013R1A1A2001950 ). Publisher Copyright: © 2014 Elsevier B.V.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

KW - 1α,25-dihydroxyviamin D

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KW - Macrophages

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