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
Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
Department of Biochemistry, College of Medicine, Korea University, Seoul, Republic of Korea.
Immunol Lett. 2015 Jan;163(1):14-21. doi: 10.1016/j.imlet.2014.11.004. Epub 2014 Nov 15.
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.
髓样细胞表达的触发受体-1（TREM-1）在人单核细胞/巨噬细胞和上皮细胞中由1α,25-二羟基维生素D3（1,25(OH)2D3）诱导产生。然而，关于1,25(OH)2D3诱导人单核细胞/巨噬细胞中TREM-1表达的机制，目前所知甚少。在本研究中，1,25(OH)2D3被证明能强烈上调佛波酯（PMA）分化的U937细胞中的缺氧诱导转录因子（HIF）。然而，HIF并非主要参与1,25(OH)2D3诱导的TREM-1表达。相反，雷帕霉素（一种哺乳动物雷帕霉素靶蛋白（mTOR）信号通路的特异性抑制剂）可抑制1,25(OH)2D3诱导的TREM-1表达，这表明mTOR参与其中。雷帕霉素也抑制了1,25(OH)2D3对HIF蛋白的诱导作用。此外，1,25(OH)2D3诱导了mTOR复合物1（mTORC1）的靶蛋白p70S6激酶的磷酸化。我们的结果表明，1,25(OH)2D3通过mTOR信号通路在人巨噬细胞中诱导TREM-1的表达。
