Journal
IMMUNOLOGY LETTERS
Volume 163, Issue 1, Pages 14-21Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.imlet.2014.11.004
Keywords
TREM-1; 1 alpha,25-dihydroxyviamin D-3; mTOR; Monocytes; Macrophages
Categories
Funding
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2013R1A1A2001950]
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Triggering receptor expressed on myeloid cells-1 (TREM-1) is induced by 1 alpha,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) in human monocytes/macrophages and epithelial cells. However, little information is available regarding the mechanism of 1,25(OH)(2)D-3-induced TREM-1 expression in human monocytes/macrophages. In this study, 1,25(OH)(2)D-3 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)(2)D-3-induced TREM-1 expression. Instead, 1,25(OH)(2)D-3-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)(2)D-3 was also inhibited by rapamycin. In addition, 1,25(OH)(2)D-3 induced the phosphorylation of p70S6 kinase, a target of mTOR complex 1 (mTORC1). Our results suggest that 1,25(OH)(2)D-3 induces the expression of TREM-1 through the mTOR signaling pathway in human macrophages. (C) 2014 Elsevier B.V. All rights reserved.
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