SHORT-TERM DEXAMETHASONE TREATMENT MODULATES THE EXPRESSION OF THE MURINE TCR-XI GENE LOCUS

Glucocorticoids (GCH) are highly effective agents in controlling infla mmation and immune response. We studied the effect of the synthetic GC H dexamethasone (DEX) on the expression of TCR zeta gene splicings tha t code for some chains belonging to the T-cell receptor (TCR)/CD3 comp lex. In the DEX-treated hybridoma T-cell line 3DO, TCR zeta gene splic ings increase within the first 24 hr (about fourfold increase), as dem onstrated by reverse transcriptase-polymerase chain reaction and RNase protection assay. This increase is due to the stimulation of TCR zeta gene locus transcription, as demonstrated by the ''run-on'' assay. A similar upregulation was observed in murine thymocytes following in vi vo DEX treatment. As a consequence of TCR zeta gene locus modulation, the expression of the spliced mRNAs coding for TCR zeta and TCR eta su bunits is increased, whereas their relative ratio is only slightly cha nged. Indeed, the amount of TCR zeta protein in 24-hr DEX-treated cell s is fivefold more than that in the untreated cells. A similar effect was seen in 3DO cells treated with hydrocortisone but not in those tre ated with testosterone. TCR zeta protein increase was confined to the cytoplasm and therefore TCR/CD3 complex expression did not increase. T his newly described effect of DEX may constitute an additional molecul ar mechanism that contributes to its immunomodulating activity. (C) 19 97 Academic Press.