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Originally published In Press as doi:10.1074/jbc.M909168199 on April 5, 2000
J. Biol. Chem., Vol. 275, Issue 27, 20260-20267, July 7, 2000
Chemokines Are the Main Proinflammatory Mediators in Human
Monocytes Activated by Staphylococcus aureus,
Peptidoglycan, and Endotoxin*
Zheng-Ming
Wang,
Chao
Liu, and
Roman
Dziarski
From the Northwest Center for Medical Education, Indiana University
School of Medicine, Gary, Indiana 46408
It is widely believed that the cytokines tumor
necrosis factor (TNF)- , interleukin (IL)-1, and IL-6 are the main
proinflammatory mediators induced in the host by bacteria and their
cell wall components. To test this hypothesis, we compared the level of expression of 600 genes activated in human monocytes by
Staphylococcus aureus, peptidoglycan, endotoxin, and
interferon- . These stimulants induced expression of over 120 genes,
as identified by cDNA arrays. The highest activated genes for
proinflammatory mediators induced by all three bacterial stimulants
were chemokine genes (IL-8 and macrophage inflammatory protein
(MIP)-1 ), whereas cytokine genes (TNF- , IL-1, and IL-6) were
induced to a lower extent. Genes for other chemokines (MIP-2 ,
MIP-1 , and monocyte chemoattractant protein-1) were also induced
higher than the cytokine genes by peptidoglycan, and as high or higher
than the cytokine genes by S. aureus and endotoxin. This
high induction of chemokine genes was confirmed by quantitative RNase
protection assay, and high secretion of chemokines was confirmed by
enzyme-linked immunosorbent assays. Although genes for chemokines were
the highest and genes for cytokines were the second highest induced
genes by all three bacterial stimulants, each stimulus induced a unique
pattern of gene expression. By contrast, expression of a completely
different gene pattern was induced by a nonbacterial stimulus,
interferon- . These results establish chemokines as the main
mediators induced by both Gram-positive and Gram-negative bacteria and
are consistent with the highly inflammatory nature of bacterial infections.
*
This work was supported by United States Public Health
Service National Institutes of Health Grant AI2879.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.
To whom correspondence should be addressed: Northwest Center for
Medical Education, Indiana University School of Medicine, 3400 Broadway, Gary, IN 46408. Tel.: 219-980-6535; Fax: 219-980-6566; E-mail: rdziar@iunhaw1.iun.indiana.edu.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.
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