Laboratory for Experimental Trauma Surgery, Justus-Liebig University, Giessen, Germany.
Life Sci. 2012 Nov 27;91(21-22):1048-52. doi: 10.1016/j.lfs.2012.04.032. Epub 2012 May 1.
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.
由于刺激存在于类风湿关节炎（RA）患者滑膜中的α7-烟碱型乙酰胆碱受体（nAChR）会导致促炎细胞因子减少，因此α7-nAChR 被认为是一个新的治疗靶点。在此背景下，我们提出了一个问题，即在 RA 滑膜样本中，α7-nAChR mRNA 是否与骨关节炎（OA）有差异表达，以及非神经元胆碱能系统的其他成分是否也存在，并在 RA 患者的滑膜中与 OA 相比存在差异表达。
使用 RT-PCR 和免疫荧光标记法，在 RA 和 OA 患者的滑膜组织样本中确定了烟碱和毒蕈碱乙酰胆碱受体（mAChRs）、胆碱和乙酰胆碱转运体、合成和降解酶的表达。
与 OA 相比，RA 患者的 nAChR 亚基β4表达增加，而亚基α2 和α4以及 mAChR M1R 的表达下降。然而，对于所有其他 nAChR 亚基和 mAChRs，RA 和 OA 患者之间没有显著差异。关于 ACh 转运体和酶，OA 和 RA 患者之间没有观察到表达变化，除了胆碱乙酰转移酶（ChAT），它只在 OA 滑膜中检测到，而在 RA 滑膜中未检测到。
我们的研究结果表明，除了α7-nAChR 之外，非神经元胆碱能系统的其他成分也存在于 RA 和 OA 患者的滑膜中，并存在差异表达，这使得它们成为开发 RA 治疗新策略的有趣替代靶点。
