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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
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Chemokines Are the Main Proinflammatory Mediators in Human Monocytes Activated by Staphylococcus aureus, Peptidoglycan, and Endotoxin*

Zheng-Ming Wang, Chao Liu, and Roman DziarskiDagger

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)-alpha , 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-gamma . 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)-1alpha ), whereas cytokine genes (TNF-alpha , IL-1, and IL-6) were induced to a lower extent. Genes for other chemokines (MIP-2alpha , MIP-1beta , 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-gamma . 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.

Dagger 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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