title: Effects of rapamycin on DC-SIGN expression and biological functions in DC.
abstract: Rapamycin, a macrolide antibiotic, has potent immunosuppressive properties as an antirejection therapy in organ transplantation. Studies show that dendritic cells (DC) are important targets for rapamycin, which can inhibit DC maturation and DC-induced allogeneic T cell proliferation. In this study, we investigated the effects of rapamycin on the expressions of DC-SIGN and transcription factor PU.1 and the function of DC. Treatment with rapamycin significantly reduced the expression of DC-SIGN in a dose-dependent manner associated with suppression of PU.1 gene expression and the ability of DC to migrate and stimulate T cell proliferation. The expression of DC-SIGN was significantly suppressed using PU.1 siRNA. Intriguingly, rapamycin treatment largely decreased the expressions of PU.1 and DC-SIGN in THP-1 cells. In addition, treatment with rapamycin down-regulated the promoter activity of DC-SIGN. In conclusion, rapamycin inhibits DC-SIGN expression and suppresses the ability of DC to migrate and stimulate T cell proliferation through the PU.1 gene transcription pathway.
authors.affiliation: Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.
authors.forename: Minchao
authors.initials: M
authors.lastname: Cai
authors.affiliation: Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, Shanghai 200025, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zou
authors.affiliation: Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Li
authors.affiliation: Shanghai Institute of Immunology, Institutes of Medical Sciences, Shanghai JiaoTong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Nie
authors.affiliation: State Key Laboratory of Medical Genomics and Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.
authors.forename: Jiuchang
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.
authors.forename: Chundi
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D017931:DNA Primers; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D007959:Lymphocyte Culture Test, Mixed; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D017931:DNA Primers; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D020123:Sirolimus; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin