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Blocking of melatonin synthesis and MT1 receptor impairs the activation of Jurkat T cells
Authors:Patricia J. Lardone  Amalia Rubio  Isabel Cerrillo  Araceli G��mez-Corvera  Antonio Carrillo-Vico  Marina Sanchez-Hidalgo  Juan M. Guerrero  Patricia Fernandez-Riejos  Victor Sanchez-Margalet  Patrocinio Molinero
Affiliation:(1) Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Department of Medical Biochemistry and Molecular Biology, University of Seville School of Medicine, Sanchez Pizjuan 4, 41009 Seville, Spain;(2) Department of Medical Biochemistry and Molecular Biology, Virgen Macarena University Hospital, University of Seville School of Medicine, Seville, Spain;(3) Department of Molecular Biology and Biochemical Engineering, University Pablo de Olavide, Seville, Spain;(4) Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Department of Clinical Biochemistry, Virgen del Rocio University Hospital, Seville, Spain
Abstract:Melatonin has been proposed as regulating the immune system by affecting cytokine production in immunocompetent cells, enhancing the production of several T helper (Th)1 cytokines. To further investigate the melatonin’s role in IL-2/IL-2R system, we established an inducible T-REx expression system in Jurkat cells in which the protein levels of HIOMT enzyme or MT1 receptor were significantly down-regulated upon tetracycline incubation. We found that T-REx Jurkat cells with lower levels of HIOMT activity, and consequently lower content of endogenous melatonin, showed IL-2 production decrease after activation with lectin. Likewise, tetracycline-inducible stable cell line expressing MT1 antisense produced decreased amounts of IL-2 (mRNA and protein levels) after stimulation. Moreover, in T-Rex-MT1 cells incubated with tetracycline, a sub-optimal PHA dose failed to induce the early activation marker CD25 on the cell surface. The results shown here support the relevance of endogenous melatonin and its signaling in T cell activation.
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