Migliorati G, Bartoli A, Nocentini G, Ronchetti S, Moraca R, Riccardi C
Department of Clinical Medicine, Pathology and Pharmacology, University of Perugia, Italy.
Mol Cell Biochem. 1997 Feb;167(1-2):135-44. doi: 10.1023/a:1006829421509.
Glucocorticoid hormones (GCH) are anti-inflammatory and immunosuppressive agents that inhibit T-cell growth and activation. Since the T-cell receptor (TCR)/CD3 complex mediates T-lymphocyte activation, we studied the effect of in vitro dexamethasone (DEX), a synthetic GCH, on TCR/CD3 expression. DEX-treatment of a hybridoma T-cell line and normal un-transformed T-cell clones induced a decrease of the TCR/ CD3 membrane expression after 4 days. After 4 weeks, TCR/CD3 was undetectable. However, the amount of mRNAs coding TCR/CD3 chains, including TCR alpha, TCR beta, CD3 gamma, CD3 theta and CD3 epsilon, as well as the amount of CD3 epsilon protein, a major component of the complex, were unaltered. By contrast, a decrease of the mRNAs deriving from the TCR zeta gene locus, as well as of the TCR zeta protein which is responsible for the membrane expression of the TCR/CD3 complex, was induced. These data suggest that the down-modulation of TCR expression is due to the diminution of TCR zeta gene products in DEX-treated cells.
糖皮质激素（GCH）是抗炎和免疫抑制药物，可抑制T细胞生长和活化。由于T细胞受体（TCR）/CD3复合物介导T淋巴细胞活化，我们研究了体外合成糖皮质激素地塞米松（DEX）对TCR/CD3表达的影响。用DEX处理杂交瘤T细胞系和正常未转化的T细胞克隆4天后，TCR/CD3膜表达下降。4周后，无法检测到TCR/CD3。然而，编码TCR/CD3链的mRNA量，包括TCRα、TCRβ、CD3γ、CD3θ和CD3ε，以及复合物的主要成分CD3ε蛋白的量均未改变。相比之下，源自TCRζ基因座的mRNA以及负责TCR/CD3复合物膜表达的TCRζ蛋白减少。这些数据表明，DEX处理的细胞中TCRζ基因产物的减少导致了TCR表达的下调。
