Human Lymphocyte-Synthesized Melatonin Is Involved in the Regulation of the Interleukin-2/Interleukin-2 Receptor System
Antonio Carrillo-Vico,
Patricia J. Lardone,
José M. Fernández-Santos,
Inés Martín-Lacave,
Juan R. Calvo,
Michal Karasek and
Juan M. Guerrero
Departments of Medical Biochemistry and Molecular Biology (A.C.-V., P.J.L., J.R.C., J.M.G.) and Normal and Pathological Cytology and Histology (J.M.F.-S., I.M.-L.), The University of Seville School of Medicine and Virgen Macarena Hospital, 41009 Seville, Spain; and Laboratory of Electron Microscopy (M.K.), Department of Pathology, Medical University of Lodz, 92-216 Lodz, Poland
Address all correspondence and requests for reprints to: Juan M. Guerrero, Department of Medical Biochemistry and Molecular Biology, The University of Seville School of Medicine, Avda. Sánchez Pizjuán 4, 41009 Seville, Spain. E-mail: guerrero{at}us.es.
Since melatonin was first isolated in 1958 up to the last fewyears, this substance was considered a hormone exclusive tothe pineal gland. Although melatonin has lately been identifiedin a large number of extrapineal sites, its potential biologicalactions have not yet been studied. This paper shows that humanlymphocyte-synthesized melatonin plays a crucial role modulatingIL-2/IL-2 receptor system because when blocking melatonin biosynthesisby the tryptophan hydroxylase inhibitor, parachlorophenylalanine,both IL-2 and IL-2 receptor levels fell, restoring them by addingexogenous melatonin. Moreover, we demonstrated that this endogenousmelatonin interfered with the exogenous melatonin effect onIL-2 production. Melatonin exerted these effects by a receptor-mediatedaction mechanism because both IL-2 and IL-2 receptor expressionssignificantly decreased when lymphocytes were incubated in thepresence of the specific membrane and/or nuclear melatonin receptorantagonists, luzindole, and/or CGP 55644, respectively. Finally,we made the real significance of the membrane melatonin receptorsin this process clear, so prostaglandin E2-induced inhibitionon IL-2 production increased when we blocked the membrane receptorsusing luzindole. In conclusion, these data show that endogenousmelatonin is an essential part for an accurate response of humanlymphocytes through the modulation of IL-2/IL-2 receptor system.
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