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J Biol Chem, Vol. 274, Issue 20, 14012-14020, May 14, 1999
From the Peptidoglycan (PGN), the major cell wall
component of Gram-positive bacteria, induces secretion of cytokines in
macrophages through CD14, the pattern recognition receptor that binds
lipopolysaccharide and other microbial products. To begin to elucidate
the mechanisms that regulate the transcription of cytokine genes, we
wanted to determine which transcription factors are activated by PGN in mouse RAW264.7 and human THP-1 macrophage cells. Our results
demonstrated that: (i) PGN induced phosphorylation of the transcription
factors ATF-1 and CREB; (ii) ATF-1 and CREB bound DNA as a dimer and
induced transcriptional activation of a CRE reporter plasmid, which was inhibited by dominant negative CREB and ATF-1; (iii) PGN induced phosphorylation of c-Jun, protein synthesis of JunB and c-Fos, and
transcriptional activation of the AP-1 reporter plasmid, which was
inhibited by dominant negative c-Fos; and (iv) PGN-induced activation
of CREB/ATF and AP-1 was mediated through CD14. This is the first study
to demonstrate activation of CREB/ATF and AP-1 transcription factors by
PGN or by any other component of Gram-positive bacteria.
Bacterial Peptidoglycan Induces CD14-dependent
Activation of Transcription Factors CREB/ATF and AP-1
,,
Northwest Center for Medical Education,
Indiana University School of Medicine, Gary, Indiana 46408 and the
¶ Laboratory of Biochemistry, NCI, National Institutes of Health,
Bethesda, Maryland 20892
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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