Blocking of melatonin synthesis and MT(1) receptor impairs the activation of Jurkat T cells.
Melatonin has been proposed as regulating the immune system by affecting cytokine production in immunocompetent cells, enhancing the production of several T helper (Th)1 cytokines. To further investigate the melatonin's role in IL-2/IL-2R system, we established an inducible T-REx expression system in Jurkat cells in which the protein levels of HIOMT enzyme or MT(1) receptor were significantly down-regulated upon tetracycline incubation. We found that T-REx Jurkat cells with lower levels of HIOMT activity, and consequently lower content of endogenous melatonin, showed IL-2 production decrease after activation with lectin. Likewise, tetracycline-inducible stable cell line expressing MT(1) antisense produced decreased amounts of IL-2 (mRNA and protein levels) after stimulation. Moreover, in T-Rex-MT(1) cells incubated with tetracycline, a sub-optimal PHA dose failed to induce the early activation marker CD25 on the cell surface. The results shown here support the relevance of endogenous melatonin and its signaling in T cell activation.
Lardone
Patricia J
PJ
Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Department of Medical Biochemistry and Molecular Biology, University of Seville School of Medicine, Sanchez Pizjuan 4, 41009, Seville, Spain.
Rubio
Amalia
A
Cerrillo
Isabel
I
Gómez-Corvera
Araceli
A
Carrillo-Vico
Antonio
A
Sanchez-Hidalgo
Marina
M
Guerrero
Juan M
JM
Fernandez-Riejos
Patricia
P
Sanchez-Margalet
Victor
V
Molinero
Patrocinio
P
D000121:Acetylserotonin O-Methyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008550:Melatonin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D044122:Receptor, Melatonin, MT1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
D007376:Interleukin-2; D044122:Receptor, Melatonin, MT1; D000121:Acetylserotonin O-Methyltransferase; D008550:Melatonin