Melatonin synthesized by Jurkat human leukemic T cell line is implicated in IL-2 production.
Human lymphocytes have recently been described as an important physiological source of melatonin (N-acetyl-5-methoxytryptamine), which could be involved in the regulation of the human immune system. On the other hand, stimulation of IL-2 production by exogenous melatonin has been shown in the Jurkat human lymphocytic cell line. Furthermore, both melatonin membrane and nuclear receptors are present in these cells. In this study, we show that the necessary machinery to synthesize melatonin is present and active in resting and stimulated Jurkat cells. Accordingly, we have found that cells synthesize and release melatonin in both conditions. Therefore, we investigated whether endogenous melatonin produced by Jurkat cells was involved in the regulation of IL-2 production. When melatonin membrane and nuclear receptors were blocked using specific antagonists, luzindole and CGP 55644, respectively, we found that IL-2 production decreased, and this drop was reverted by exogenous melatonin. Additionally, PHA activation of Jurkat cells changed the profile of melatonin nuclear receptor mRNA expression. A previous study showed that exogenous melatonin is able to counteract the decrease in IL-2 production caused by prostaglandin E2 (PGE2) in human lymphocytes via its membrane receptor. In our model, when we blocked the melatonin membrane receptor with luzindole, the inhibitory effect of PGE2 on IL-2 production was higher. Therefore, we have demonstrated the physiological role of endogenous melatonin in this cell line. These findings indicate that endogenous melatonin synthesized by human T cells would contribute to regulation of its own IL-2 production, acting as an intracrine, autocrine, and/or paracrine substance.
Lardone
Patricia J
PJ
Department of Medical Biochemistry and Molecular Biology, School of Medicine and Virgen Macarena Hospital, University of Seville, Seville, Spain.
Carrillo-Vico
Antonio
A
Naranjo
María C
MC
De Felipe
Beatriz
B
Vallejo
Alejandro
A
Karasek
Michal
M
Guerrero
Juan M
JM
D000121:Acetylserotonin O-Methyltransferase / Q000235:genetics / Q000378:metabolism; D047068:Arylalkylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D019169:Jurkat Cells; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008550:Melatonin / Q000096:biosynthesis*; D010835:Phytohemagglutinins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D044094:Receptors, Melatonin / Q000235:genetics / Q000378:metabolism; D014363:Tryptamines / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007376:Interleukin-2; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D044094:Receptors, Melatonin; D014363:Tryptamines; C057154:luzindole; D000121:Acetylserotonin O-Methyltransferase; D047068:Arylalkylamine N-Acetyltransferase; D008550:Melatonin; D015232:Dinoprostone