The proliferation of human T lymphoblastic cells induced by 5-HT1B receptors activation is regulated by 5-HT-moduline

Serotonin (5-hydroxytryptamine, 5-HT) is a well-known neurotransmitter and immunomodulator, which has been reported to affect the function of cells in the immune system. The purpose of the herein reported experiments was to investigate whether serotonin could regulate the proliferation of a human T lymphoblastic leukemia cell line (CCRF-CEM cells) and to characterize the 5-HT receptor(s) involved in this phenomenon using a pharmacological approach. The herein presented results show that serotonin alone stimulated the proliferation of CCRF-CEM cells and that this effect could be mimicked by two 5-HT_1B/1D receptor agonists (L-694,247 and GR 46611). Serotonin- or L-694,247-induced increase in cell proliferation was inhibited by a selective 5-HT_1B receptor antagonist, SB-224289. A recently identified endogenous tetrapeptide, 5-HT-moduline (Leu–Ser–Ala–Leu, LSAL), which specifically antagonizes 5-HT_1B/1D receptor activity, was also shown to reverse the stimulating action of L-694,247 on T cell proliferation. Taken together, these results establish the existence of a direct serotonergic control of the T cell proliferation mediated through h5-HT_1B receptors. In addition, these results are in favour of an immunomodulatory role of 5-HT-moduline.