1 alpha,25-Dihydroxyvitamin D-3 upregulates HIF-1 and TREM-1 via mTOR signaling
- Authors
- Lee, Bitnara; Kwon, Eunji; Kim, Yongjin; Kim, Jin Hee; Son, Sang Wook; Lee, Jin Kyu; Kim, Dong Won; Sohn, Jeongwon; Kim, Tae-Hwan; Ji, Jong Dae
- Issue Date
- Jan-2015
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- TREM-1; 1 alpha,25-dihydroxyviamin D-3; mTOR; Monocytes; Macrophages
- Citation
- IMMUNOLOGY LETTERS, v.163, no.1, pp.14 - 21
- Indexed
- SCIE
SCOPUS
- Journal Title
- IMMUNOLOGY LETTERS
- Volume
- 163
- Number
- 1
- Start Page
- 14
- End Page
- 21
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/158116
- DOI
- 10.1016/j.imlet.2014.11.004
- ISSN
- 0165-2478
- Abstract
- 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.
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