Acetylcholine Receptor Alpha Subunit Mrna Expression In Human Thymus: Augmented Expression In Myasthenia Gravis And Upregulation By Interferon-Gamma

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 receptor (AChR alpha), P3A(-) and P3A(+), in thymus tissue obtained from MG and control subjects an da 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 mRNA as 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 bot isoforms in MG than in control thymus. Expression of both isoforms in TEC9 was enhanced significantly by treatment with interferon-gamma whereas IL-1 alpha, IL-4, and IL-6 had no effect. Thus, there is differential regulation of AChR alpha variants in thymus and TEC relative to muscle and interferon-gamma represents a novel regulator of AChR alpha mRNA expression. MG thymus is distinguished by increased expression of both isoforms of this autoantigen, a finding that ma reflect enhancement of transcription by local microenvironmental factors. (C) 1999 Academic Press.