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.
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Received 23 September 2008; received after revision 19 November 2008; accepted 21 November 2008
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Lardone, P.J., Carrillo-Vico, A., Molinero, P. et al. A novel interplay between membrane and nuclear melatonin receptors in human lymphocytes: significance in IL-2 production. Cell. Mol. Life Sci. 66, 516 (2009). https://doi.org/10.1007/s00018-008-8601-5
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DOI: https://doi.org/10.1007/s00018-008-8601-5