A novel interplay between membrane and nuclear melatonin receptors in human lymphocytes: significance in IL-2 production.
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.
Lardone
P J
PJ
Department of Medical Biochemistry and Molecular Biology, University of Seville School of Medicine, 41013 Seville, Spain.
Carrillo-Vico
A
A
Molinero
P
P
Rubio
A
A
Guerrero
J M
JM
D000328:Adult; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D019169:Jurkat Cells; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism*; D008550:Melatonin / Q000378:metabolism; D008875:Middle Aged; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D044094:Receptors, Melatonin / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D014363:Tryptamines / Q000378:metabolism
D007376:Interleukin-2; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; C539738:RORA protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D015534:Trans-Activators; D014363:Tryptamines; C057154:luzindole; D000242:Cyclic AMP; D008550:Melatonin; D015232:Dinoprostone