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and Lipopolysaccharide in Macrophages Is Regulated by STAT11
Department of Microbiology and Immunology, Indiana University School of Medicine, and Walther Cancer Institute, Indianapolis, IN 46202
Proper regulation of the Tap-1 gene is critical for the initiation
and continuation of a cellular immune response. Analysis of the
Tap-1/low molecular mass polypeptide 2 bidirectional promoter showed
that the IFN-
activation site element is critical for the rapid
induction of the promoter by IFN- following transfection into the
human macrophage cell line THP-1. Furthermore, activation of STAT1
binding to this site was important for the synergistic response seen
following the stimulation with both IFN- and LPS. Mutation of an
IFN-stimulated regulatory element that binds IFN regulatory factor 1
appeared to enhance the response to IFN- and LPS. These data show
that STAT1 is necessary for the activation of Tap-1 gene expression in
APCs and initiation of cellular immune responses. Furthermore, our data
suggest that bacterial products such as LPS may enhance cellular immune
responses through augmenting the ability of STAT1 to regulate
IFN--inducible genes.
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