title: Morphine Suppresses T helper Lymphocyte Differentiation to Th1 Type Through PI3K/AKT Pathway.
abstract: To investigate the effect of morphine on T helper lymphocyte differentiation and PI3K/AKT pathway mechanism, CD4+ lymphocytes were treated by phorbol-myristate-acetate (25 ng/ml) (PMA) plus ionomycin (1 μg/ml) in the presence of various concentrations of morphine (25, 50, 100, 200 ng/ml) for 4 h. Th1 and Th2 subsets, supernatant cytokines, and PI3K, AKT, and protein kinase C-theta (PKC-θ) levels were detected. The Th1 cell percentage, Th1-derived cytokines, and ratio of Th1/Th2 decreased in the presence of morphine in a concentration-dependent manner. However, Th2 cell percentage kept stable after morphine treatment. The phosphorylation of PI3K and AKT decreased, but the phosphorylation of PKC-θ did not change in the presence of morphine. The decreased percentage of Th1 cells and ratio of Th1/Th2 was recovered by naloxone concentration-dependently. Morphine can inhibit the differentiation of Th1 lymphocytes and decrease the ratio of Th1/Th2 via the pathway of PI3K/AKT. The effect can be inhibited by naloxone.
authors.affiliation: Department of Anesthesiology, Nanjing Maternal and Child Health Hospital, Nanjing, China.
authors.forename: Mao
authors.initials: M
authors.lastname: Mao
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital with Nanjing Medical University, No. 300, Guangzhou road, Nanjing, 210029, People's Republic of China.
authors.forename: Yanning
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital with Nanjing Medical University, No. 300, Guangzhou road, Nanjing, 210029, People's Republic of China. dgsunjie@hotmail.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015759:Ionomycin / Q000633:toxicity; D007527:Isoenzymes / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D000074121:Protein Kinase C-theta; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000633:toxicity; D018417:Th1 Cells / Q000166:cytology*; D058408:Th1-Th2 Balance / Q000187:drug effects*; D018418:Th2 Cells / Q000166:cytology*
chemical_list: D007527:Isoenzymes; D015847:Interleukin-4; D009270:Naloxone; D015759:Ionomycin; C016658:phorbolol myristate acetate; D009020:Morphine; D007371:Interferon-gamma; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D013755:Tetradecanoylphorbol Acetate
keywords: PI3K/AKT; PKC-θ; T helper lymphocyte; Th1 cell; morphine