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TGF-beta suppresses IFN-gamma induction of class II MHC gene expression by inhibiting class II transactivator messenger RNA expression.
J Immunol. 1997 Mar 01; 158(5):2065-75.JI

Abstract

Recently, a non-DNA binding protein, class II transactivator (CIITA), has been shown to be required for constitutive and IFN-gamma-inducible class II MHC transcription. The cytokine TGF-beta inhibits IFN-gamma-induced class II MHC expression at the transcriptional level. In this study, we provide evidence that TGF-beta blocks IFN-gamma-induced CIITA mRNA accumulation. TGF-beta down-regulates class II MHC and CIITA mRNA 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 inhibitory effect of TGF-beta on class II MHC was abrogated, but the cells remained responsive for expression of TGF-beta-inducible genes. Cell lines that possessed defects in TGF-beta signaling also became refractory to inhibition of IFN-gamma-induced CIITA and class II MHC expression. Our data indicate that TGF-beta suppresses IFN-gamma-induced class II MHC expression by inhibiting accumulation of CIITA mRNA.

Authors+Show Affiliations

Department of Cell Biology, University of Alabama at Birmingham, 35294, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9036950

Citation

Lee, Y J., et al. "TGF-beta Suppresses IFN-gamma Induction of Class II MHC Gene Expression By Inhibiting Class II Transactivator Messenger RNA Expression." Journal of Immunology (Baltimore, Md. : 1950), vol. 158, no. 5, 1997, pp. 2065-75.
Lee YJ, Han Y, Lu HT, et al. TGF-beta suppresses IFN-gamma induction of class II MHC gene expression by inhibiting class II transactivator messenger RNA expression. J Immunol. 1997;158(5):2065-75.
Lee, Y. J., Han, Y., Lu, H. T., Nguyen, V., Qin, H., Howe, P. H., Hocevar, B. A., Boss, J. M., Ransohoff, R. M., & Benveniste, E. N. (1997). TGF-beta suppresses IFN-gamma induction of class II MHC gene expression by inhibiting class II transactivator messenger RNA expression. Journal of Immunology (Baltimore, Md. : 1950), 158(5), 2065-75.
Lee YJ, et al. TGF-beta Suppresses IFN-gamma Induction of Class II MHC Gene Expression By Inhibiting Class II Transactivator Messenger RNA Expression. J Immunol. 1997 Mar 1;158(5):2065-75. PubMed PMID: 9036950.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TGF-beta suppresses IFN-gamma induction of class II MHC gene expression by inhibiting class II transactivator messenger RNA expression. AU - Lee,Y J, AU - Han,Y, AU - Lu,H T, AU - Nguyen,V, AU - Qin,H, AU - Howe,P H, AU - Hocevar,B A, AU - Boss,J M, AU - Ransohoff,R M, AU - Benveniste,E N, PY - 1997/3/1/pubmed PY - 1997/3/1/medline PY - 1997/3/1/entrez SP - 2065 EP - 75 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 158 IS - 5 N2 - Recently, a non-DNA binding protein, class II transactivator (CIITA), has been shown to be required for constitutive and IFN-gamma-inducible class II MHC transcription. The cytokine TGF-beta inhibits IFN-gamma-induced class II MHC expression at the transcriptional level. In this study, we provide evidence that TGF-beta blocks IFN-gamma-induced CIITA mRNA accumulation. TGF-beta down-regulates class II MHC and CIITA mRNA 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 inhibitory effect of TGF-beta on class II MHC was abrogated, but the cells remained responsive for expression of TGF-beta-inducible genes. Cell lines that possessed defects in TGF-beta signaling also became refractory to inhibition of IFN-gamma-induced CIITA and class II MHC expression. Our data indicate that TGF-beta suppresses IFN-gamma-induced class II MHC expression by inhibiting accumulation of CIITA mRNA. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/9036950/TGF_beta_suppresses_IFN_gamma_induction_of_class_II_MHC_gene_expression_by_inhibiting_class_II_transactivator_messenger_RNA_expression_ L2 - https://www.jimmunol.org/lookup/pmidlookup?view=long&pmid=9036950 DB - PRIME DP - Unbound Medicine ER -