Zheng Y, Wheatley L M, Liu T, Levinson A I
Section of Allergy and Immunology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Clin Immunol. 1999 May;91(2):170-7. doi: 10.1006/clim.1999.4689.
Previous studies by us and others have demonstrated the expression of acetylcholine receptors on epithelial cells in the thymus of myasthenia gravis (MG) and control subjects. In the present experiments, we used a reverse transcription-polymerase chain reaction (RT-PCR) to analyze the profile of the two major isoforms of the alpha chain of these receptors (AChRalpha), P3A- and P3A+, in thymus tissue obtained from MG and control subjects and a human thymic epithelial cell line (TEC9). In addition, using a semiquantitative RT-PCR, we compared the amounts of P3A- and P3A+ mRNA expressed in thymic tissue obtained from these two sources and determined if their expression in TEC9 is modulated by cytokines. We found that mRNAs encoding P3A- and P3A+ are expressed at approximately a 5:1 ratio in both MG and control thymus tissue. This contrasts with skeletal muscle where mRNAs encoding these isoforms are expressed equally. A pattern of preferential P3A- vs P3A+ mRNA expression was also observed in TEC9. We observed 2.8-fold greater expression of both isoforms in MG than in control thymus. Expression of both isoforms in TEC9 was enhanced significantly by treatment with interferon-gamma whereas IL-1alpha, IL-4, and IL-6 had no effect. Thus, there is differential regulation of AChRalpha variants in thymus and TEC relative to muscle and interferon-gamma represents a novel regulator of AChRalpha mRNA expression. MG thymus is distinguished by increased expression of both isoforms of this autoantigen, a finding that may reflect enhancement of transcription by local microenvironmental factors.
我们和其他研究人员之前的研究已证实，重症肌无力（MG）患者及对照者胸腺的上皮细胞上存在乙酰胆碱受体表达。在本实验中，我们运用逆转录-聚合酶链反应（RT-PCR），分析了从MG患者、对照者以及人胸腺上皮细胞系（TEC9）获取的胸腺组织中，这些受体α链的两种主要亚型（AChRα），即P3A-和P3A+的表达情况。此外，我们通过半定量RT-PCR，比较了从这两个来源获取的胸腺组织中P3A-和P3A+ mRNA的表达量，并确定细胞因子是否会调节它们在TEC9中的表达。我们发现，在MG患者和对照者的胸腺组织中，编码P3A-和P3A+的mRNA表达比例约为5:1。这与骨骼肌中编码这些亚型的mRNA等量表达形成对比。在TEC9中也观察到了P3A-与P3A+ mRNA表达的偏好模式。我们发现，MG患者胸腺中这两种亚型的表达均比对照者胸腺高2.8倍。用γ干扰素处理后TEC9中这两种亚型的表达均显著增强，而IL-1α、IL-4和IL-6则无此作用。因此，相对于肌肉而言，胸腺和TEC中AChRα变体存在差异调节，γ干扰素是AChRα mRNA表达的一种新调节因子。MG患者的胸腺以该自身抗原两种亚型的表达增加为特征，这一发现可能反映了局部微环境因素对转录的增强作用。
