Rhythmic expression of the melatonergic biosynthetic pathway and its differential modulation in vitro by LPS and IL10 in bone marrow and spleen.

ABSTRACT

Daily oscillation of the immune system follows the central biological clock outputs control such as melatonin produced by the pineal gland. Despite the literature showing that melatonin is also synthesized by macrophages and T lymphocytes, no information is available regarding the temporal profile of the melatonergic system of immune cells and organs in steady-state. Here, the expression of the enzymes arylalkylamine-N-acetyltransferase (AA-NAT), its phosphorylated form (P-AA-NAT) and acetylserotonin-O-methyltransferase (ASMT) were evaluated in phagocytes and T cells of the bone marrow (BM) and spleen. We also determined how the melatonergic system of these cells is modulated by LPS and the cytokine IL-10. The expression of the melatonergic enzymes showed daily rhythms in BM and spleen cells. Melatonin rhythm in the BM, but not in the spleen, follows P-AA-NAT daily variation. In BM cells, LPS and IL10 induced an increase in melatonin levels associated with the increased expressions of P-AA-NAT and ASMT. In spleen cells, LPS induced an increase in the expression of P-AA-NAT but not of melatonin. Conversely, IL10 induced a significant increase in melatonin production associated with increased AA-NAT/P-AA-NAT expressions. In conclusion, BM and spleen cells present different profiles of circadian production of local melatonin and responses to immune signals.