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Papers In Press, published online ahead of print May 22, 2000
Dept. of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294
Corresponding Author: Tika{at}uab.edu
CD40 is a cell surface receptor belonging to the TNF-receptor family that plays a critical role in the regulation of immune responses. We have previously shown that the cytokine IFN-
J. Biol. Chem, 10.1074/jbc.M002482200
Submitted on March 23, 2000
Revised on May 19, 2000
Accepted on May 22, 2000
Involvement of STAT-1 and Ets Family Members in IFN-
Induction of CD40 Transcription in Microglia/Macrophages
induces CD40 expression in microglia. Herein, we have elucidated the molecular mechanisms underlying IFN- induction of CD40 gene expression in microglia/macrophages. IFN- upregulates CD40 expression at the transcriptional level, and this regulation involves the STAT-1
transcription factor. Microglia from STAT-1 deficient mice were refractive to IFN- induction of CD40 expression, illustrating the importance of STAT-1 in this response. Functional analysis of the CD40 promoter indicates that two GAS elements as well as two Ets elements are involved in IFN- induction of CD40 promoter activity. STAT-1 binds to the GAS elements, while PU.1 and/or Spi-B bind to the Ets elements. The expression of PU.1 and Spi-B, in conjuction with STAT-1 activation, correlates with IFN- induciblity of CD40 expression. Collectively, our data demonstrate the involvement of STAT-1, PU.1 and Spi-B in IFN- induction of CD40 gene expression in cells of the macrophage lineage.
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