title: 5,6-dihydro-2H-pyranones and 5,6-dihydro-2H-pyridones and their derivatives modulate in vitro human T lymphocyte function.
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.
authors.affiliation: Department of Chemistry, Laboratory of Catalysis and Synthesis in Organic Chemistry, Faculty of Sciences, Abou-Bekr Belkaïd University, Tlemcen, Algeria.
authors.forename: Y Baba
authors.initials: YB
authors.lastname: Hamed
authors.forename: A
authors.initials: A
authors.lastname: Medjdoub
authors.forename: B Mostefa
authors.initials: BM
authors.lastname: Kara
authors.forename: H
authors.initials: H
authors.lastname: Merzouk
authors.forename: D
authors.initials: D
authors.lastname: Villemin
authors.forename: M
authors.initials: M
authors.lastname: Narce
mesh_terms: D000328:Adult; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007769:Lactams / Q000138:chemical synthesis / Q000494:pharmacology*; D007783:Lactones / Q000138:chemical synthesis / Q000494:pharmacology*; D008297:Male; D015162:Micronucleus Tests; D018384:Oxidative Stress; D050050:Protein Carbonylation / Q000187:drug effects; D011728:Pyridones / Q000138:chemical synthesis / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
chemical_list: D016207:Cytokines; D007769:Lactams; D007783:Lactones; D011728:Pyridones; D006861:Hydrogen Peroxide; D005978:Glutathione