Short-Term Dexamethasone Treatment Modulates the Expression of the Murine TCRζ Gene Locus

Glucocorticoids (GCH) are highly effective agents in controlling inflammation and immune response. We studied the effect of the synthetic GCH dexamethasone (DEX) on the expression of TCRζ gene splicings that code for some chains belonging to the T-cell receptor (TCR)/CD3 complex. In the DEX-treated hybridoma T-cell line 3DO, TCRζ gene splicings increase within the first 24 hr (about fourfold increase), as demonstrated by reverse transcriptase–polymerase chain reaction and RNase protection assay. This increase is due to the stimulation of TCRζ gene locus transcription, as demonstrated by the “run-on” assay. A similar upregulation was observed in murine thymocytes followingin vivoDEX treatment. As a consequence of TCRζ gene locus modulation, the expression of the spliced mRNAs coding for TCRζ and TCRη subunits is increased, whereas their relative ratio is only slightly changed. Indeed, the amount of TCRζ protein in 24-hr DEX-treated cells is fivefold more than that in the untreated cells. A similar effect was seen in 3DO cells treated with hydrocortisone but not in those treated with testosterone. TCRζ protein increase was confined to the cytoplasm and therefore TCR/CD3 complex expression did not increase. This newly described effect of DEX may constitute an additional molecular mechanism that contributes to its immunomodulating activity.