[Background and objective]
Mast cells, the cells responsible for both immediate and delayed allergic reactions, are also one of the few melatonin-producing cells in the body. Melatonin, which is primarily released from the pineal gland and regulates circadian rhythm, has both hypnotic and antioxidant effects. However, the physiological function of melatonin produced by mast cells is unknown. We set out to investigate this phenomenon.
[Methods]
LAD2, a human-derived mast cell line, was used in all experiments. Melatonin production by mast cells was detected by ELISA using anti-melatonin antibodies. mRNA and protein expression of melatonin synthase proteins were analyzed by real-time PCR and Western blotting, respectively. Allergic stimulation of the cells was performed by sensitizing the cells with 1.0 μg/mL anti-NP IgE, followed by stimulation with 1.3 μg/mL NP-BSA.
[Results]
Expression of arylalkylamine N-acetyltransferase (AANAT) and hydroxyindole-O-methyltransferase (HIOMT), key enzymes in melatonin production, was upregulated more than 2-fold at both mRNA and protein levels in mast cells treated by allergic-stimuli. The expression of the two enzymes was also upregulated by A23187, a calcium ionophore; however, the upregulation level was less than 2-fold for each enzyme. Conversely, mRNA and protein expression of both enzymes was slightly reduced in cells pre-treated with 500 μM db-cAMP, which is known to increase cAMP.
[Discussion]
These results indicate during mast cell degranulation, representing an increase in intracellular calcium concentration, the expression of melatonin-producing enzymes is increased during resynthesis of the granules. However, IgE-mediated degranulation by allergic stimulation results in more production of melatonin than it is required for replacement, therefore contributing to the repair of damaged tissues.