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 acety lcholine receptors on epithelial cells in the thymus of myasthenia gravis ( MG) and control subjects. In the present experiments, we used a reverse tra nscription-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 semiquantit ative RT-PCR, we compared the amounts of P3A(-) and P3A(+) mRNA expressed i n thymic tissue obtained from these two sources and determined if their exp ression 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 co ntrol thymus tissue. This contrasts with skeletal muscle where mRNA as enco ding 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 inte rferon-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 relativ e to muscle and interferon-gamma represents a novel regulator of AChR alpha mRNA expression. MG thymus is distinguished by increased expression of bot h isoforms of this autoantigen, a finding that ma reflect enhancement of tr anscription by local microenvironmental factors. (C) 1999 Academic Press.