A novel interplay between membrane and nuclear melatonin receptors in human lymphocytes: significance in IL-2 production |
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| Authors: | P. J. Lardone A. Carrillo-Vico P. Molinero A. Rubio J. M. Guerrero |
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| Affiliation: | (1) Department of Medical Biochemistry and Molecular Biology, University of Seville School of Medicine, 41013 Seville, Spain;(2) Department of Clinical Biochemistry, Virgen del Rocío University Hospital (IBiS/CSIC/Seville University), Avda. Manuel Siurot S/N, 41013 Seville, Spain |
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| Abstract: | Human lymphocyte melatonin, through membrane and nuclear receptors binding, acts as an activator in IL-2 production. Antagonism of membrane melatonin receptors using luzindole exacerbates the drop of the IL-2 production induced by PGE2 in peripheral blood mononuclear and Jurkat cells. This paper studies the melatonin membrane and nuclear receptors interplay in PGE2-diminished IL-2 production. The decrease in IL-2 production after PGE2 and/or luzindole administration correlated with downregulation in the nuclear receptor RORα. We also highlighted a role of cAMP in the pathway, because forskolin mimicked the effects of luzindole and/or PGE2 in the RORα expression. Finally, a significant RORα downregulation was observed in T cells permanently transfected with inducible MT1 antisense. In conclusion, we show a novel connection between melatonin membrane receptor signalling and RORα expression, opening a new way to understand melatonin regulation in lymphocyte physiology. Received 23 September 2008; received after revision 19 November 2008; accepted 21 November 2008 |
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| Keywords: | KeywordHeading" >. Melatonin receptors RORalpha cAMP melatonin MT1 |
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