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IL-1 beta inhibits IFN-gamma-induced class II MHC expression by suppressing transcription of the class II transactivator gene.
J Immunol. 1999 Jan 15; 162(2):886-96.JI

Abstract

Class II MHC Ags are critical for the initiation of immune responses by presenting Ag to T lymphocytes, leading to their activation and differentiation. The transcriptional activation of class II MHC genes requires the induction of the class II transactivator (CIITA) protein, a master regulator that is essential for both constitutive and IFN-gamma-inducible class II MHC expression. The cytokine IL-1beta has been shown to inhibit IFN-gamma-induced class II MHC expression in various cell types. We investigated the underlying mechanism of this inhibitory effect of IL-1beta using human astroglioma cell lines. Our findings demonstrate that IL-1beta prevents the expression of class II MHC mRNA and protein upon treatment with IFN-gamma. Furthermore, we demonstrate that IFN-gamma induction of CIITA mRNA expression is inhibited by treatment of cells with IL-1beta. IL-1beta suppressed IFN-gamma activation of the type IV CIITA promoter in astroglioma cells, indicating that the inhibitory influence of IL-1beta is mediated by inhibition of CIITA transcription. IL-1beta did not interfere with IFN-gamma receptor signal transduction, since tyrosine phosphorylation, nuclear translocation, and DNA binding of STAT-1alpha to an IFN-gamma activation sequence of the type IV CIITA promoter were not affected by IL-1beta. As well, IL-1beta treatment did not affect the ability of IFN-gamma-induced interferon-regulatory factor-1 (IRF-1) to bind the IRF-1 element within the type IV CIITA promoter. This study suggests that IL-1beta may play a role in regulating immunoreactivity by inhibiting transcription of the CIITA gene, thereby reducing subsequent class II MHC expression.

Authors+Show Affiliations

Department of Physiology and Biophysics, University of Alabama, Birmingham 35294, USA.No 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

9916712

Citation

Rohn, W, et al. "IL-1 Beta Inhibits IFN-gamma-induced Class II MHC Expression By Suppressing Transcription of the Class II Transactivator Gene." Journal of Immunology (Baltimore, Md. : 1950), vol. 162, no. 2, 1999, pp. 886-96.
Rohn W, Tang LP, Dong Y, et al. IL-1 beta inhibits IFN-gamma-induced class II MHC expression by suppressing transcription of the class II transactivator gene. J Immunol. 1999;162(2):886-96.
Rohn, W., Tang, L. P., Dong, Y., & Benveniste, E. N. (1999). IL-1 beta inhibits IFN-gamma-induced class II MHC expression by suppressing transcription of the class II transactivator gene. Journal of Immunology (Baltimore, Md. : 1950), 162(2), 886-96.
Rohn W, et al. IL-1 Beta Inhibits IFN-gamma-induced Class II MHC Expression By Suppressing Transcription of the Class II Transactivator Gene. J Immunol. 1999 Jan 15;162(2):886-96. PubMed PMID: 9916712.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IL-1 beta inhibits IFN-gamma-induced class II MHC expression by suppressing transcription of the class II transactivator gene. AU - Rohn,W, AU - Tang,L P, AU - Dong,Y, AU - Benveniste,E N, PY - 1999/1/23/pubmed PY - 1999/1/23/medline PY - 1999/1/23/entrez SP - 886 EP - 96 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 162 IS - 2 N2 - Class II MHC Ags are critical for the initiation of immune responses by presenting Ag to T lymphocytes, leading to their activation and differentiation. The transcriptional activation of class II MHC genes requires the induction of the class II transactivator (CIITA) protein, a master regulator that is essential for both constitutive and IFN-gamma-inducible class II MHC expression. The cytokine IL-1beta has been shown to inhibit IFN-gamma-induced class II MHC expression in various cell types. We investigated the underlying mechanism of this inhibitory effect of IL-1beta using human astroglioma cell lines. Our findings demonstrate that IL-1beta prevents the expression of class II MHC mRNA and protein upon treatment with IFN-gamma. Furthermore, we demonstrate that IFN-gamma induction of CIITA mRNA expression is inhibited by treatment of cells with IL-1beta. IL-1beta suppressed IFN-gamma activation of the type IV CIITA promoter in astroglioma cells, indicating that the inhibitory influence of IL-1beta is mediated by inhibition of CIITA transcription. IL-1beta did not interfere with IFN-gamma receptor signal transduction, since tyrosine phosphorylation, nuclear translocation, and DNA binding of STAT-1alpha to an IFN-gamma activation sequence of the type IV CIITA promoter were not affected by IL-1beta. As well, IL-1beta treatment did not affect the ability of IFN-gamma-induced interferon-regulatory factor-1 (IRF-1) to bind the IRF-1 element within the type IV CIITA promoter. This study suggests that IL-1beta may play a role in regulating immunoreactivity by inhibiting transcription of the CIITA gene, thereby reducing subsequent class II MHC expression. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/9916712/IL_1_beta_inhibits_IFN_gamma_induced_class_II_MHC_expression_by_suppressing_transcription_of_the_class_II_transactivator_gene_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=9916712 DB - PRIME DP - Unbound Medicine ER -