Effect of dexamethasone on T-cell receptor/CD3 expression.
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.
Migliorati
G
G
Department of Clinical Medicine, Pathology and Pharmacology, University of Perugia, Italy.
Bartoli
A
A
Nocentini
G
G
Ronchetti
S
S
Moraca
R
R
Riccardi
C
C
D000818:Animals; D015153:Blotting, Western; D017252:CD3 Complex / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation; D005938:Glucocorticoids / Q000494:pharmacology; D008565:Membrane Proteins / Q000187:drug effects / Q000235:genetics; D051379:Mice; D012326:RNA Splicing; D012333:RNA, Messenger / Q000096:biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects / Q000235:genetics; D014158:Transcription, Genetic
D017252:CD3 Complex; D005938:Glucocorticoids; D008565:Membrane Proteins; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain; D003907:Dexamethasone