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5,6-Dihydro-2H-pyranones and 5,6-dihydro-2H-pyridones and their derivatives modulate in vitro human T lymphocyte function

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Abstract

The aim of this work was to study the in vitro effects of δ-lactone 1, δ-lactam 3 and their enaminone derivatives 2 and 4, synthesized in our laboratory, on the proliferative responses of human lymphocytes, Th1 and Th2 cytokine secretion and intracellular redox status. Peripheral blood lymphocytes were isolated using differential centrifugation on a density gradient of Histopaque. They were cultured with mitogen concanavalin A (Con A) and with different concentrations of the compounds 1, 2, 3 and 4 (0.1–10 μM). Proliferation (MTT assay), IL-2, INFγ and IL-4 (Elisa kits), oxidative markers (intracellular glutathione, hydroperoxide and carbonyl protein contents) and cytotoxic effect (micronucleus test) were determined. The compounds 1 and 2 are immunosuppressive and decrease IL-2, INFγ and IL-4 secretion with a shift away from Th2 response to Th1 phenotype. The compounds 3 and 4 were immunostimulant and increased cytokine secretion with a shift away from Th1 response to Th2. The introduction of an enamine group to 1 and 3 to provide 2 and 4 seemed to attenuate their immunological properties. These immunomodulatory properties were, however, accompanied by an increase in lymphocyte intracellular oxidative stress, especially with 1 and 2 at high concentrations. In conclusion, the compounds 1, 2, 3 and 4 could be used to provide cell-mediated immune responses for novel therapies in T-cell mediated immune disorders.

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Acknowledgments

This work was supported by the French Foreign Office (International Research Extension Grant TASSILI 08MDU723) and by the Algerian Research Investigation Office (CNEPRU, PNR).

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Authors and Affiliations

  1. Department of Chemistry, Laboratory of Catalysis and Synthesis in Organic Chemistry, Faculty of Sciences, BP119, Abou-Bekr Belkaïd University, Tlemcen, 13000, Algeria

    Y. Baba Hamed & B. Mostefa Kara

  2. Department of Biology, Laboratory of Physiology, Physiopathology and Biochemistry of Nutrition, Faculty of Natural and Life Sciences, Earth and Universe, Abou-Bekr Belkaïd University, Tlemcen, 13000, Algeria

    A. Medjdoub & H. Merzouk

  3. ENSICAEN, LCMT-UMR 6507 CNRS, Université de Caen, 14050, Caen, France

    D. Villemin

  4. Faculty of Life, Earth and Environment Sciences, INSERM UMR 866, Lipids Nutrition Cancer, University of Burgundy, Dijon, 21000, France

    M. Narce

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  1. Y. Baba Hamed
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  2. A. Medjdoub
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Correspondence to H. Merzouk.

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Hamed, Y.B., Medjdoub, A., Kara, B.M. et al. 5,6-Dihydro-2H-pyranones and 5,6-dihydro-2H-pyridones and their derivatives modulate in vitro human T lymphocyte function. Mol Cell Biochem 360, 23–33 (2012). https://doi.org/10.1007/s11010-011-1040-x

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  • DOI: https://doi.org/10.1007/s11010-011-1040-x

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