Nizri Eran, Hamra-Amitay Yasmine, Sicsic Camille, Lavon Iris, Brenner Talma
Laboratory of Neuroimmunology, Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Medical Center, P.O. Box 12000, Jerusalem 91120, Israel.
Neuropharmacology. 2006 Apr;50(5):540-7. doi: 10.1016/j.neuropharm.2005.10.013. Epub 2005 Dec 5.
We investigated the anti-inflammatory effects of acetylcholinesterase inhibitors (AChEI) at the cellular and molecular levels. AChEI suppressed lymphocyte proliferation and pro-inflammatory cytokine production, as well as extracellular esterase activity. Anti-inflammatory activity was mediated by the alpha7 nicotinic acetylcholine receptor (neuronal); the muscarinic receptor had the opposite effect. Treatment of the central nervous system (CNS) inflammatory disease, experimental autoimmune encephalomyelitis (EAE), with EN101, an anti-sense oligodeoxynucleotide, targeted to AChE mRNA, reduced the clinical severity of the disease and CNS inflammation intensity. The results of our experiments suggest that AChEI increase the concentration of extracellular acetylcholine (ACh), rendering it available for interaction with a nicotinic receptor expressed on lymphocytes. Our findings point to a novel role for AChEI which may be relevant in CNS inflammatory diseases such as EAE and multiple sclerosis. They also emphasize the importance of cholinergic balance in neurological disorders, such as Alzheimer's disease and myasthenia gravis, in which these drugs are used.
我们在细胞和分子水平上研究了乙酰胆碱酯酶抑制剂（AChEI）的抗炎作用。AChEI抑制淋巴细胞增殖、促炎细胞因子产生以及细胞外酯酶活性。抗炎活性由α7烟碱型乙酰胆碱受体（神经元型）介导；毒蕈碱型受体则具有相反作用。用靶向AChE mRNA的反义寡脱氧核苷酸EN101治疗中枢神经系统（CNS）炎性疾病——实验性自身免疫性脑脊髓炎（EAE），可降低疾病的临床严重程度和CNS炎症强度。我们的实验结果表明，AChEI可提高细胞外乙酰胆碱（ACh）的浓度，使其能够与淋巴细胞上表达的烟碱型受体相互作用。我们的研究结果指出了AChEI的一种新作用，这可能与EAE和多发性硬化症等CNS炎性疾病相关。它们还强调了胆碱能平衡在诸如阿尔茨海默病和重症肌无力等神经系统疾病中的重要性，而这些药物正是用于治疗这些疾病的。
