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.
authors.affiliation: Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
authors.forename: Bitnara
authors.initials: B
authors.lastname: Lee
authors.affiliation: Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
authors.forename: Eunji
authors.initials: E
authors.lastname: Kwon
authors.affiliation: Department of Biochemistry, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Yongjin
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Dermatology, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Dermatology, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sang Wook
authors.initials: SW
authors.lastname: Son
authors.affiliation: Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
authors.forename: Jin Kyu
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
authors.forename: Dong Won
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Jeongwon
authors.initials: J
authors.lastname: Sohn
authors.affiliation: Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea. Electronic address: thkim@hanyang.ac.kr.
authors.forename: Tae-Hwan
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Rheumatology, College of Medicine, Korea University, 126-1, Anam-Dong 5-Ga, Sungbuk-Ku, Seoul 136-705, Republic of Korea. Electronic address: jjdjmesy@korea.ac.kr.
authors.forename: Jong Dae
authors.initials: JD
authors.lastname: Ji
mesh_terms: D002117:Calcitriol / Q000494:pharmacology*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000096:biosynthesis* / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000276:immunology; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D058570:TOR Serine-Threonine Kinases / Q000276:immunology / Q000378:metabolism*; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D020298:U937 Cells; D015854:Up-Regulation / Q000187:drug effects* / Q000276:immunology; D014815:Vitamins / Q000494:pharmacology*
chemical_list: D051793:Hypoxia-Inducible Factor 1; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014815:Vitamins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D002117:Calcitriol
keywords: 1α,25-dihydroxyviamin D(3); Macrophages; Monocytes; TREM-1; mTOR