The Non-neuronal Cholinergic System: Roles of Muscarinic Acetylcholine Receptors in Interleukin-2 Synthesis in Lymphocytes

Abstract

Receptors for many neurotransmitters including catecholamines and acetylcholine (ACh) have been detected on the cell surface of lymphocytes. It has been demonstrated that a human T cell line synthesizes ACh and suggested that ACh may be an autacoid modulating T cell-dependent immune responses. However, the biochemical interactions of the ACh system with the immune system have not been elucidated in detail. We have shown that m1 and m2 muscarinic receptor mRNAs are expressed in human peripheral blood lymphocytes and in human T cell line Jurkat cells and that pretreatment of these cells with a muscarinic receptor agonist enhances interleukin-2 (IL-2) production. We also postulated possible intracellular signaling pathways via which muscarinic receptors regulate IL-2 production in Jurkat cells. The findings suggest that M1 muscarinic receptors are involved in muscarinic receptor-mediated enhancement of IL-2 production in Jurkat cells and that the transcription factor AP-1 and pathways via mitogen-activated protein kinase (MAPK)/extracellular signal regulated protein kinase and c-Jun N-terminal kinase, but not via p38 MAPK, may be involved in the muscarinic receptor-mediated enhancement of IL-2 production. Our findings demonstrate a neuro-immune interaction through muscarinic receptor signaling in immune cells.