TGF-BETA SUPPRESSES IFN-GAMMA INDUCTION OF CLASS-II MHC GENE-EXPRESSION BY INHIBITING CLASS-II TRANSACTIVATOR MESSENGER-RNA EXPRESSION

Citation
Yj. Lee et al., TGF-BETA SUPPRESSES IFN-GAMMA INDUCTION OF CLASS-II MHC GENE-EXPRESSION BY INHIBITING CLASS-II TRANSACTIVATOR MESSENGER-RNA EXPRESSION, The Journal of immunology, 158(5), 1997, pp. 2065-2075
Citations number
66
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
The Journal of immunology
ISSN journal
0022-1767 → ACNP
Volume
158
Issue
5
Year of publication
1997
Pages
2065 - 2075
Database
ISI
SICI code
0022-1767(1997)158:5<2065:TSIIOC>2.0.ZU;2-9
Abstract
Recently, a non-DNA binding protein, class II transactivator (CIITA), has been shown to be required for constitutive and INF-gamma-inducible class II MHC transcription. The cytokine TGF-beta inhibits INF-gamma- induced class II MHC expression at the transcriptional level. In this study, we provide evidence that TGF-beta blocks INF-gamma-induced CIIT A mRNA accumulation. TGF-beta down-regulates class II MHC and CIITA mR NA accumulation in human astroglioma and fibrosarcoma cell lines, but TGF-beta does not destabilize the CIITA message, suggesting an effect at the transcriptional level. In cells that stably overexpressed CIITA , leading to a constitutive class II MHC-positive phenotype, the inhib itory effect of TGF-beta on class II MHC was abrogated, but the cells remained responsive for expression of TGF-beta-inducible genes. Cell l ines that possessed defects in TGF-beta signaling also became refracto ry to inhibition of INF-gamma-induced CIITA and class II MHC expressio n, Our data indicate that TGF-beta suppresses INF-gamma-induced class II MHC expression by inhibiting accumulation of CIITA mRNA.