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  • dexamethasone  (1)
  • glucocorticoid hormones  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Molecular and cellular biochemistry 167 (1997), S. 135-144 
    ISSN: 1573-4919
    Keywords: glucocorticoid hormones ; T lymphocytes ; T-cell receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract 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 TCRα, TCRβ, CD3γ, CD3δ and CD3ε, as well as the amount of CD3ε protein, a major component of the complex, were unaltered. By contrast, a decrease of the mRNAs deriving from the TCRζ gene locus, as well as of the TCRζ 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 TCRζ gene products in DEX-treated cells. (Mol Cell Biochem 167: 135-144, 1997)
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-4919
    Keywords: T-cell receptor (TCR) ; TCRζ gene locus ; dexamethasone ; glucocorticoids ; splicing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract T-cell receptor (TCR) is a multichain receptor in which the TCRζ subunit is important for membrane assembly and signal transduction. Four alternative splicings of the murine TCRζ gene locus have been previously described. We here describe a new alternative splicing of murine TCRζ gene, TCRκ, cloned by RT-PCR, that is encoded by exons 1-7, a portion of exon 9 and the whole exon 10 of TCRζ gene. The protein encoded by TCRκ mRNA is identical to that encoded by TCRκ mRNA, because the stop codon is present in the exon 9 before splicing with exon 10. RNAse protection assays carried out on total RNA from thymocytes indicate that TCRκ mRNA is 1 half with respect to TCRκ mRNA, suggesting that TCRκ mRNA contributes to determine the TCRκ protein levels. The 3′ untranslated region of TCRκ mRNA is different from that of TCRκ and this might lead to different t1/2 for each species in vivo. We also show that dexamethasone (DEX), a synthetic glucocorticoid hormone, increases the amount of TCRκ in the hybridoma T-cell line 3DO (about 5-fold increase), as indicated by reverse transcriptase-polymerase chain reaction (RT-PCR) and RNAse protection assays. This newly described effect of DEX may constitute a further molecular mechanism that contributes to its immunomodulating activity.
    Type of Medium: Electronic Resource
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