Beta endorphin regulates NK and NKT cell functions via distinct pathways



Problem:  Opioid induced regulation of the mucosal immune system has been reported. We examined effects of β-endorphin on large granular lymphocyte cell lines to investigate regulatory roles of placenta derived β-endorphin on local immune system.

Materials and Methods:  Large granular lymphocyte cell lines KHYG-1 (NK) and MOTN-1 (NKT) were maintained in RPMI1640 supplemented with 10% FCS. IFN-γ1 production was evaluated by ELISPOT assay under stimulation with IL-2 (100 IU/mL) and/or IL-12 (10 IU/mL). Various concentrations of β-endorphin were added into culture media with and without opioid antagonist naloxone.

Results:  MOTN-1 expressed opioid receptor κ and constitutively produced IFN-γ1. Production was up-regulated by IL-2 and/or IL-12. β-endorphin suppressed constitutive and IL-2 induced IFN-γ1 production while it showed no effects on IL-12 induced IFN-γ1 production. Suppression was completely abrogated by simultaneous naloxone treatment. KHYG-1 expressed none of 3 opioid receptors and showed non-constitutive IFN-γ1 secretion. β-endorphin up-regulated production in low concentrations while down-regulated production at high concentrations. This regulation was not affected by naloxone.

Conclusion:  β-endorphin suppress IL-2/STAT5 induced signaling of large granular NKT lymphocyte cell line MOTN-1 while it affects large granular NK lymphocyte cell line KHYG-1 via opioid receptor independent pathways.