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

Autor: Michel Narce, Didier Villemin, Y. Baba hamed, Amel Medjdoub, B. Mostefa Kara, Hafida Merzouk
Přispěvatelé: Laboratoire de chimie moléculaire et thioorganique (LCMT), Centre National de la Recherche Scientifique (CNRS)-Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU), Domaine expérimental agri-environnement, Inst. Méditerranéen du Patrimoine Cynégétique et Faunistique
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Adult
Male
Lactams
medicine.drug_class
Pyridones
Lymphocyte
In vitro proliferation
T-Lymphocytes
Clinical Biochemistry
Pharmacology
Immunostimulant
Protein Carbonylation
03 medical and health sciences
Lactones
0302 clinical medicine
Immune system
Human lymphocytes
medicine
Humans
MTT assay
Molecular Biology
Cells
Cultured
ComputingMilieux_MISCELLANEOUS
030304 developmental biology
Cell Proliferation
0303 health sciences
Micronucleus Tests
biology
d-Lactams
[CHIM.ORGA]Chemical Sciences/Organic chemistry
Cell Biology
General Medicine
T lymphocyte
d-Lactones
Hydrogen Peroxide
[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences
Glutathione
3. Good health
Oxidative Stress
medicine.anatomical_structure
Biochemistry
Concanavalin A
Oxidative stress
030220 oncology & carcinogenesis
biology.protein
Cytokines
Cytokine secretion
Female
Intracellular
Zdroj: Molecular and Cellular Biochemistry
Molecular and Cellular Biochemistry, Springer Verlag, 2012, 360 (1-2), pp.23-33. ⟨10.1007/s11010-011-1040-x⟩
ISSN: 0300-8177
1573-4919
Popis: 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.
Databáze: OpenAIRE
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