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Morphine Suppresses T helper Lymphocyte Differentiation to Th1 Type Through PI3K/AKT Pathway

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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.

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Acknowledgments

Dr. Jie Sun is an assistant fellow at the collaborative innovation center for cardiovascular disease translational medicine. We thank Genbao Feng, from Nanjing University, P.R. China, for his technical assistance.

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Correspondence to Jie Sun.

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The study was supported by the National Natural Science Foundation of China (no. 30801068). This study was also supported by A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). We do not have any other competing interest.

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Mao, M., Qian, Y. & Sun, J. Morphine Suppresses T helper Lymphocyte Differentiation to Th1 Type Through PI3K/AKT Pathway. Inflammation 39, 813–821 (2016). https://doi.org/10.1007/s10753-016-0310-x

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