title: Dexmedetomidine Inhibits Maturation and Function of Human Cord Blood-Derived Dendritic Cells by Interfering with Synthesis and Secretion of IL-12 and IL-23.
abstract: OBJECTIVE
  To investigate the effects and underlying mechanism of dexmedetomidine on the cultured human dendritic cells (DCs).
  
  
  METHODS
  Human DCs and cytotoxic T lymphocytes (CTLs) were obtained from human cord blood mononuclear cells by density gradient centrifugation. Cultured DCs were divided into three groups: dexmedetomidine group, dexmedetomidine plus yohimbine (dexmedetomidine inhibitor) group and control group. DCs in the three groups were treated with dexmedetomidine, dexmedetomidine plus yohimbine and culture medium, respectively. After washing, the DCs were co-incubated with cultured CTLs. The maturation degree of DCs was evaluated by detecting (1) the ratios of HLA-DR-, CD86-, and CD80-positive cells (flow cytometry), and (2) expression of IL-12 and IL-23 (PCR and Elisa). The function of DCs was evaluated by detecting the proliferation (MTS assay) and cytotoxicity activity (the Elisa of IFN-γ) of CTLs. In addition, in order to explore the mechanisms of dexmedetomidine modulating DCs, α2-adrenergic receptor and its downstream signals in DCs were also detected.
  
  
  RESULTS
  The ratios of HLA-DR-, CD86-, and CD80-positive cells to total cells were similar among the three groups (P>0.05). Compared to the control group, the protein levels of IL-12 and IL-23 in the culture medium and the mRNA levels of IL-12 p35, IL-12 p40 and IL-23 p19 in the DCs all decreased in dexmedetomidine group (P<0.05). In addition, the proliferation of CTLs and the secretion of IFN-γ also decreased in the dexmedetomidine group, compared with the control group (P<0.05). Moreover, these changes induced by dexmedetomidine in the dexmedetomidine group were reversed by α2-adrenergic receptor inhibitor yohimbine in the dexmedetomidine plus yohimbine group. It was also found the decrease of mRNA levels of IL-12 p35, IL-12 p40 and IL-23 p19 in the dexmedetomidine group could be reversed by ERK1/2 or AKT inhibitors.
  
  
  CONCLUSIONS
  Dexmedetomidine could negatively modulate human immunity by inhibiting the maturation of DCs and then decreasing the proliferation and cytotoxicity activity of CTLs. The α2-adrenergic receptors and its downstream molecules ERK1/2 and AKT are closely involved in the modulation of dexmedetomidine on DCs.
authors.affiliation: Department of Anesthesiology, the Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Gong
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, the Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Le
authors.affiliation: Department of Anesthesiology, the Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, the Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Gong
authors.affiliation: Department of Anesthesiology, the Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, the Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Yunli
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, the Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Liao
authors.affiliation: Department of Anesthesiology, the Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Kaiming
authors.initials: K
authors.lastname: Duan
authors.affiliation: Department of Anesthesiology, the Third Xiangya Hospital of Central South University, Changsha, Hunan, China.|Center for Experimental Medicine, the Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Jianbin
authors.initials: J
authors.lastname: Tong
authors.affiliation: Department of Anesthesiology, the Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Ouyang
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D020927:Dexmedetomidine / Q000494:pharmacology*; D005312:Fetal Blood / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism*; D053759:Interleukin-23 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D053759:Interleukin-23; D012333:RNA, Messenger; D018664:Interleukin-12; D020927:Dexmedetomidine