Dexmedetomidine Inhibits Maturation and Function of Human Cord Blood-Derived Dendritic Cells by Interfering with Synthesis and Secretion of IL-12 and IL-23
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{"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", "type"=>"journal", "authors"=>[{"first_name"=>"Gong", "last_name"=>"Chen", "scopus_author_id"=>"57188956800"}, {"first_name"=>"Yuan", "last_name"=>"Le", "scopus_author_id"=>"55414185700"}, {"first_name"=>"Lei", "last_name"=>"Zhou", "scopus_author_id"=>"57199016259"}, {"first_name"=>"Li", "last_name"=>"Gong", "scopus_author_id"=>"56542495800"}, {"first_name"=>"Xiaoxiao", "last_name"=>"Li", "scopus_author_id"=>"56245880900"}, {"first_name"=>"Yunli", "last_name"=>"Li", "scopus_author_id"=>"56457178600"}, {"first_name"=>"Qin", "last_name"=>"Liao", "scopus_author_id"=>"35759447000"}, {"first_name"=>"Kaiming", "last_name"=>"Duan", "scopus_author_id"=>"21739358800"}, {"first_name"=>"Jianbin", "last_name"=>"Tong", "scopus_author_id"=>"37062172200"}, {"first_name"=>"Wen", "last_name"=>"Ouyang", "scopus_author_id"=>"37122512300"}], "year"=>2016, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84964355630", "pui"=>"609703288", "pmid"=>"27054340", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0153288", "sgr"=>"84964355630"}, "id"=>"45c621ed-16c6-3324-a359-da39b88be1ae", "abstract"=>"AIMS: To investigate the effects and underlying mechanism of dexmedetomidine on the cultured human dendritic cells (DCs).\\n\\nMETHODS: 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.\\n\\nRESULTS: 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.\\n\\nCONCLUSION: 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.", "link"=>"http://www.mendeley.com/research/dexmedetomidine-inhibits-maturation-function-human-cord-bloodderived-dendritic-cells-interfering-syn", "reader_count"=>5, "reader_count_by_academic_status"=>{"Researcher"=>2, "Student > Ph. D. Student"=>1, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Researcher"=>2, "Student > Ph. D. Student"=>1, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Agricultural and Biological Sciences"=>3, "Medicine and Dentistry"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}}, "group_count"=>0}

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  • {"files"=>["https://ndownloader.figshare.com/files/4927648", "https://ndownloader.figshare.com/files/4927663", "https://ndownloader.figshare.com/files/4927672"], "description"=>"<div><p>Aims</p><p>To investigate the effects and underlying mechanism of dexmedetomidine on the cultured human dendritic cells (DCs).</p><p>Methods</p><p>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.</p><p>Results</p><p>The ratios of HLA-DR-, CD86-, and CD80-positive cells to total cells were similar among the three groups (<i>P</i>>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 (<i>P</i><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 (<i>P</i><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.</p><p>Conclusion</p><p>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.</p></div>", "links"=>[], "tags"=>["cytotoxicity activity", "AKT", "control group", "PCR", "IFN", "Methods Human DCs", "cytotoxic T lymphocytes", "Dexmedetomidine Inhibits Maturation", "IL", "mRNA levels", "CTL", "density gradient centrifugation", "dexmedetomidine group", "culture medium", "dexmedetomidine modulating DCs", "ERK", "MTS"], "article_id"=>3164320, "categories"=>["Biochemistry", "Cell Biology", "Molecular Biology", "Physiology", "Pharmacology", "Chemical Sciences not elsewhere classified", "Immunology", "Developmental Biology", "Marine Biology", "Cancer", "Infectious Diseases", "Virology"], "users"=>["Gong Chen", "Yuan Le", "Lei Zhou", "Li Gong", "Xiaoxiao Li", "Yunli Li", "Qin Liao", "Kaiming Duan", "Jianbin Tong", "Wen Ouyang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0153288.s001", "https://dx.doi.org/10.1371/journal.pone.0153288.s002", "https://dx.doi.org/10.1371/journal.pone.0153288.s003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Dexmedetomidine_Inhibits_Maturation_and_Function_of_Human_Cord_Blood_Derived_Dendritic_Cells_by_Interfering_with_Synthesis_and_Secretion_of_IL_12_and_IL_23/3164320", "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", "pos_in_sequence"=>1, "defined_type"=>4, "published_date"=>"2016-04-07 05:14:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/4927720"], "description"=>"<p>(A), (B) and (C) showed mRNA levels of IL-12 p35, IL-12 p40 and IL-23 p19, respectively. (D) and (E) showed the protein levels of IL-12 and IL-23, respectively. “DEX” is short for dexmedetomidine, “YOH” is short for yohimbine. Immature DCs were differentiated in the absence or presence of different doses of DEX (1ng/ml, 2ng/ml and 4ng/ml) and yohimbine (4ng/ml, 8ng/ml and 16ng/ml) for 1 day before matured with TNF-α (“-”means do not add DEX or yohimbine). Grouping is consistent in these bar charts. The data were expressed as mean±SD of the results from these experiments. #: <i>P</i><0.05, compared to the control group; *: <i>P</i><0.05, compared to the relative DEX only group.</p>", "links"=>[], "tags"=>["cytotoxicity activity", "AKT", "control group", "PCR", "IFN", "Methods Human DCs", "cytotoxic T lymphocytes", "Dexmedetomidine Inhibits Maturation", "IL", "mRNA levels", "CTL", "density gradient centrifugation", "dexmedetomidine group", "culture medium", "dexmedetomidine modulating DCs", "ERK", "MTS"], "article_id"=>3164368, "categories"=>["Biochemistry", "Cell Biology", "Molecular Biology", "Physiology", "Pharmacology", "Chemical Sciences not elsewhere classified", "Immunology", "Developmental Biology", "Marine Biology", "Cancer", "Infectious Diseases", "Virology"], "users"=>["Gong Chen", "Yuan Le", "Lei Zhou", "Li Gong", "Xiaoxiao Li", "Yunli Li", "Qin Liao", "Kaiming Duan", "Jianbin Tong", "Wen Ouyang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153288.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Effect_of_DEX_on_IL_12_and_IL_23_production_in_mature_DCs_/3164368", "title"=>"Effect of DEX on IL-12 and IL-23 production in mature DCs.", "pos_in_sequence"=>3, "defined_type"=>1, "published_date"=>"2016-04-07 05:14:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/4927774"], "description"=>"<p>(A) mRNA expressions of α2A and α2B receptors in DCs. Abbreviations: <i>ADRA2A</i> (α2A receptor); <i>ADRA2B</i> (α2B receptor); <i>ADRA2C</i> (α2C receptor); <i>ACTB</i> (actin beta); (B) immunostaining of α2A receptors of immature DCs and mature DCs (magnification ×400).</p>", "links"=>[], "tags"=>["cytotoxicity activity", "AKT", "control group", "PCR", "IFN", "Methods Human DCs", "cytotoxic T lymphocytes", "Dexmedetomidine Inhibits Maturation", "IL", "mRNA levels", "CTL", "density gradient centrifugation", "dexmedetomidine group", "culture medium", "dexmedetomidine modulating DCs", "ERK", "MTS"], "article_id"=>3164419, "categories"=>["Biochemistry", "Cell Biology", "Molecular Biology", "Physiology", "Pharmacology", "Chemical Sciences not elsewhere classified", "Immunology", "Developmental Biology", "Marine Biology", "Cancer", "Infectious Diseases", "Virology"], "users"=>["Gong Chen", "Yuan Le", "Lei Zhou", "Li Gong", "Xiaoxiao Li", "Yunli Li", "Qin Liao", "Kaiming Duan", "Jianbin Tong", "Wen Ouyang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153288.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Expression_of_2_adrenoceptors_/3164419", "title"=>"Expression of α2-adrenoceptors.", "pos_in_sequence"=>5, "defined_type"=>1, "published_date"=>"2016-04-07 05:14:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/4927747"], "description"=>"<p>(A) Showing the CTLs proliferation via MTS assay. (B) Showing IFN-γ secretion of CTLs via Elisa detection. CTLs were co-cultured with DCs pretreated with different doses of DEX or yohimbine. The data were expressed as mean±SD. #: <i>P</i><0.05, compared to the control group; *: <i>P</i><0.05, compared to the relative DEX only group.</p>", "links"=>[], "tags"=>["cytotoxicity activity", "AKT", "control group", "PCR", "IFN", "Methods Human DCs", "cytotoxic T lymphocytes", "Dexmedetomidine Inhibits Maturation", "IL", "mRNA levels", "CTL", "density gradient centrifugation", "dexmedetomidine group", "culture medium", "dexmedetomidine modulating DCs", "ERK", "MTS"], "article_id"=>3164392, "categories"=>["Biochemistry", "Cell Biology", "Molecular Biology", "Physiology", "Pharmacology", "Chemical Sciences not elsewhere classified", "Immunology", "Developmental Biology", "Marine Biology", "Cancer", "Infectious Diseases", "Virology"], "users"=>["Gong Chen", "Yuan Le", "Lei Zhou", "Li Gong", "Xiaoxiao Li", "Yunli Li", "Qin Liao", "Kaiming Duan", "Jianbin Tong", "Wen Ouyang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153288.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Effects_of_DEX_treated_DCs_on_co_cultured_CTLs_proliferation_and_IFN_production_/3164392", "title"=>"Effects of DEX-treated DCs on co-cultured CTLs proliferation and IFN-γ production.", "pos_in_sequence"=>4, "defined_type"=>1, "published_date"=>"2016-04-07 05:14:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/4927693"], "description"=>"<p>(A) Examples of immature and mature DCs. Immature DCs showed multiple spiculated edges. Mature DCs were veiled or dendritic spine-like at semi-suspension state; (B) Flow cytometry identification of mature DCs: the ratios of CD11c-, HLA-DR-, CD86-, and CD80-positive cells to total cells were 77.7%, 83.4%, 74.9% and 67.8%, respectively.</p>", "links"=>[], "tags"=>["cytotoxicity activity", "AKT", "control group", "PCR", "IFN", "Methods Human DCs", "cytotoxic T lymphocytes", "Dexmedetomidine Inhibits Maturation", "IL", "mRNA levels", "CTL", "density gradient centrifugation", "dexmedetomidine group", "culture medium", "dexmedetomidine modulating DCs", "ERK", "MTS"], "article_id"=>3164347, "categories"=>["Biochemistry", "Cell Biology", "Molecular Biology", "Physiology", "Pharmacology", "Chemical Sciences not elsewhere classified", "Immunology", "Developmental Biology", "Marine Biology", "Cancer", "Infectious Diseases", "Virology"], "users"=>["Gong Chen", "Yuan Le", "Lei Zhou", "Li Gong", "Xiaoxiao Li", "Yunli Li", "Qin Liao", "Kaiming Duan", "Jianbin Tong", "Wen Ouyang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153288.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Identification_of_human_DCs_/3164347", "title"=>"Identification of human DCs.", "pos_in_sequence"=>2, "defined_type"=>1, "published_date"=>"2016-04-07 05:14:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/4927798"], "description"=>"<p>(A) ERK1/2 and p-ERK1/2 expressions: immature DCs were cultured in the absence or presence of DEX (2ng/ml), yohimbine (8ng/ml) and PD98059 (40μM). After 30 min, cells were harvested to test protein levels of ERK1/2 and p-ERK1/2; (B) AKT and p-AKT expressions: immature DCs were cultured in the absence or presence of DEX (2ng/ml), yohimbine (8ng/ml) and LY294002 (30μM). After 30 min, cells were harvested to test protein levels of AKT and p-AKT; (C) p38 and p-p38 expressions: immature DCs were cultured in the absence or presence of DEX (2ng/ml), yohimbine (8ng/ml) and SB203580 (30μM). After 30 min, cells were harvested to test protein levels of p38 and p-p38. (D) Immature DCs were cultured in the absence or presence of PD98059 (40Μ) for 30 min, followed by treatment with DEX (2ng/ml) for 30 min, then matured with TNF-α (100ng/ml). After 24hrs, cells were collected to test mRNA levels of IL-12 p35, IL-12 p40 and IL-23 p19; (E) Immature DCs were cultured in the absence or presence of LY294002 (30Μ) for 30 min, followed by treatment with DEX (2ng/ml) for 30 min, then matured with TNF-α (100ng/ml). After 24hrs, cells were collected to test mRNA levels of IL-12 p35, IL-12 p40 and IL-23 p19. The results are presented as mean±SD. *<i>P</i><0.05.</p>", "links"=>[], "tags"=>["cytotoxicity activity", "AKT", "control group", "PCR", "IFN", "Methods Human DCs", "cytotoxic T lymphocytes", "Dexmedetomidine Inhibits Maturation", "IL", "mRNA levels", "CTL", "density gradient centrifugation", "dexmedetomidine group", "culture medium", "dexmedetomidine modulating DCs", "ERK", "MTS"], "article_id"=>3164443, "categories"=>["Biochemistry", "Cell Biology", "Molecular Biology", "Physiology", "Pharmacology", "Chemical Sciences not elsewhere classified", "Immunology", "Developmental Biology", "Marine Biology", "Cancer", "Infectious Diseases", "Virology"], "users"=>["Gong Chen", "Yuan Le", "Lei Zhou", "Li Gong", "Xiaoxiao Li", "Yunli Li", "Qin Liao", "Kaiming Duan", "Jianbin Tong", "Wen Ouyang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153288.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/ERK1_2_AKT_and_p38_in_human_DCs_/3164443", "title"=>"ERK1/2, AKT and p38 in human DCs.", "pos_in_sequence"=>6, "defined_type"=>1, "published_date"=>"2016-04-07 05:14:07"}

PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2016-01-01T00:00:00Z", "end_date"=>"2016-12-31T00:00:00Z", "subject_areas"=>[]}
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