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-Induced Class II MHC Expression by Suppressing Transcription of the Class II Transactivator Gene1
Departments of
*
Physiology and Biophysics and
Cell Biology, University of Alabama, Birmingham, AL 35294
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-
-inducible class II MHC expression. The
cytokine IL-1ß has been shown to inhibit IFN--induced class II MHC
expression in various cell types. We investigated the underlying
mechanism of this inhibitory effect of IL-1ß using human astroglioma
cell lines. Our findings demonstrate that IL-1ß prevents the
expression of class II MHC mRNA and protein upon treatment with
IFN-. Furthermore, we demonstrate that IFN- induction of
CIITA mRNA expression is inhibited by treatment of cells with IL-1ß.
IL-1ß suppressed IFN- activation of the type IV CIITA promoter in
astroglioma cells, indicating that the inhibitory influence of IL-1ß
is mediated by inhibition of CIITA transcription. IL-1ß did not
interfere with IFN- receptor signal transduction, since tyrosine
phosphorylation, nuclear translocation, and DNA binding of STAT-1
to
an IFN- activation sequence of the type IV CIITA promoter were not
affected by IL-1ß. As well, IL-1ß treatment did not affect the
ability of IFN--induced interferon-regulatory factor-1
(IRF-1) to bind the IRF-1 element within the type IV CIITA
promoter. This study suggests that IL-1ß may play a role in
regulating immunoreactivity by inhibiting transcription of the CIITA
gene, thereby reducing subsequent class II MHC
expression.
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