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J. Biol. Chem., Vol. 275, Issue 31, 23674-23684, August 4, 2000
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From the Department of Cell Biology, The Univeristy of Alabama at
Birmingham, Birmingham, Alabama 35294-0005
Cluster of differentiation (CD)-40 is a
cell surface receptor belonging to the tumor necrosis factor
receptor family that plays a critical role in the regulation of immune
responses. We have previously shown that the cytokine interferon
(IFN)-
Involvement of STAT-1 and Ets Family Members in Interferon-
Induction of CD40 Transcription in Microglia/Macrophages*
and
induces CD40 expression in microglia. Herein, we have
elucidated the molecular mechanisms underlying IFN- induction of
CD40 gene expression in microglia/macrophages. IFN- up-regulates
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 gamma
activated sequence elements as well as two Ets elements are involved in
IFN- induction of CD40 promoter activity. STAT-1 binds to the
gamma activated sequence elements, whereas 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- inducibility 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.
*
This work was supported by National Multiple Sclerosis
Society Grant RG-2205-B-9 (to E. N. B.), National Institutes
of Health Grant NS-36765 (to E. N. B.), and Grant AM-20614
from the University of Alabama at Birmingham Flow Cytometry Core
Facility.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Supported by a National Institutes of Health Predoctoral
Fellowship T32AI-07493.
§
To whom correspondence should be addressed: Dept. of Cell Biology,
MCLM 350, The University of Alabama at Birmingham, 1918 University
Blvd., Birmingham, AL 35294-0005. Tel.: 205-934-7667; Fax:
205-975-6748; E-mail: tika@uab.edu.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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