1141101609 Beta endorphin regulates NK and NKT cell functions via distinct pathways

Abstract

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.