A novel interplay between membrane and nuclear melatonin receptors in human lymphocytes: significance in IL-2 production

• DOI: 10.1007/s00018-008-8601-5
• Publication Date: 2008-12-19T07:02:32Z
• Authors: P. J. Lardone; A. Carrillo-Vico; P. Molinero; A. Rubio; J. M. Guerrero
• Keywords: Adult; Cell Nucleus; 0301 basic medicine; MT1; RORalpha; Cell Membrane; Receptors, Melatonin; Receptors, Cytoplasmic and Nuclear; Nuclear Receptor Subfamily 1, Group F, Member 1; Middle Aged; Dinoprostone; Tryptamines; Jurkat Cells; 03 medical and health sciences; cAMP; Cyclic AMP; Trans-Activators; Animals; Humans; Interleukin-2; Lymphocytes; Melatonin receptors; Melatonin

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 PGE(2) in peripheral blood mononuclear and Jurkat cells. This paper studies the melatonin membrane and nuclear receptors interplay in PGE(2)-diminished IL-2 production. The decrease in IL-2 production after PGE(2) and/or luzindole administration correlated with downregulation in the nuclear receptor RORalpha. We also highlighted a role of cAMP in the pathway, because forskolin mimicked the effects of luzindole and/or PGE(2) in the RORalpha expression. Finally, a significant RORalpha downregulation was observed in T cells permanently transfected with inducible MT(1) antisense. In conclusion, we show a novel connection between melatonin membrane receptor signalling and RORalpha expression, opening a new way to understand melatonin regulation in lymphocyte physiology.