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Expression of the non-neuronal cholinergic system in human knee synovial tissue from patients with rheumatoid arthritis and osteoarthritis.

机译:类风湿性关节炎和骨关节炎患者人膝关节胆碱组织中非神经元胆碱能系统的表达。

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As the stimulation of the α7-nicotinic acetylcholine receptor (nAChR), which is present in the synovium of patients with rheumatoid arthritis (RA), leads to a decrease in pro-inflammatory cytokines, the α7-nAChR is being discussed as a new therapeutic target. On this background we addressed the question whether α7-nAChR mRNA was differentially expressed in RA compared to osteoarthritis (OA) synovial samples and whether other components of the non-neuronal cholinergic system were also present and differentially expressed in the synovium of patients with RA in comparison to OA.The expression of nicotinic and muscarinic acetylcholine receptors (mAChRs), choline and acetylcholine transporters, synthesising and degrading enzymes was determined in human samples of synovial tissue from patients with RA and OA using RT-PCR and immunofluorescence labelling.Compared to OA, patients with RA showed increased expression of nAChR subunit β4 while a decline in subunits α2 and α4 as well as in mAChR M1R was observed. For all other nAChR subunits and mAChRs however there was no significant difference between RA and OA patients. With regard to the ACh transporters and enzymes no expressional changes were observed between OA and RA patients, except for the choline acetyltransferase (ChAT) which was only detected in OA but not in RA synovium.Our results indicate that besides α7-nAChR other components of the non-neuronal cholinergic system are present and differentially expressed in the synovium of RA and OA patients, which makes them interesting alternative targets in the development of new strategies for RA therapy.
机译:作为刺激存在于类风湿性关节炎(RA)患者的α7-烟碱乙酰胆碱受体(NACHR)的刺激,导致促炎细胞因子的降低,α7-NACHR正在讨论为新的治疗方法目标。在该背景下,与骨关节炎(OA)滑膜样品相比,在RA中差异表达α7-NACHR mRNA和非神经元胆碱能系统的其他组分是否也存在并在患者患者的患者中表达的问题与OA患者的人类样品,使用RT-PCR和免疫荧光凝固患者的人类样品中测定烟碱和毒蕈酰乙酰胆碱受体(MACKRS),胆碱和乙酰胆碱转运蛋白的表达,胆碱和乙酰胆碱转运蛋白,合成和降解酶。 RA患者显示NACHR亚基β4的表达增加,而亚基α2和α4以及MACHR M1R的下降。对于所有其他NACHR亚基和MACHR,RA和OA患者之间没有显着差异。关于ACH转运蛋白和酶没有在OA和RA患者之间观察到的表现变化,除了仅在OA中检测到但不在RA Synovium中检测到的胆碱乙酰转移酶(聊天)。除了α7-NACHR其他组件之外非神经元胆碱能系统在RA和OA患者的Synovovium中存在和差异表达,这使得它们在制定RA治疗的新策略方面使其成为有趣的替代目标。

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