Short-term dexamethasone treatment modulates the expression of the murine TCR zeta 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 TCR zeta 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, TCR zeta 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 TCR zeta gene locus transcription, as demonstrated by the "run-on" assay. A similar upregulation was observed in murine thymocytes following in vivo DEX treatment. As a consequence of TCR zeta gene locus modulation, the expression of the spliced mRNAs coding for TCR zeta and TCR eta subunits is increased, whereas their relative ratio is only slightly changed. Indeed, the amount of TCR zeta 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. TCR zeta 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.
Ronchetti
S
S
Department of Clinical Medicine, Pathology and Pharmacology (DMCPF), Perugia University Medical School, Italy.
Nocentini
G
G
Giunchi
L
L
Bartoli
A
A
Moraca
R
R
Riccardi
C
C
Migliorati
G
G
D000818:Animals; D017252:CD3 Complex / Q000235:genetics*; D002451:Cell Compartmentation / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013739:Testosterone / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D017252:CD3 Complex; D005938:Glucocorticoids; D008565:Membrane Proteins; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; C094053:antigen T cell receptor, iota chain; C054979:antigen T cell receptor, zeta chain; D013739:Testosterone; D003907:Dexamethasone; D006854:Hydrocortisone