Journal of Biological Chemistry
Volume 272, Issue 52, 26 December 1997, Pages 32910-32918
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NUCLEIC ACIDS, PROTEIN SYNTHESIS, AND MOLECULAR GENETICS
Differential Regulation of Interleukin-8 and Intercellular Adhesion Molecule-1 by H2O2 and Tumor Necrosis Factor-α in Endothelial and Epithelial Cells*

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The reactive oxygen intermediate H2O2 can function as a signaling molecule to activate gene expression. In this study, we demonstrate that oxidant stress induced by tumor necrosis factor α (TNFα) or H2O2 differentially regulates intercellular adhesion molecule-1 (ICAM-1) and interleukin-8 (IL-8) gene expression in endothelial and epithelial cells. Northern blot analysis revealed that TNFα induced both ICAM-1 and IL-8 expression in either the A549 lung epithelial cell line or the human microvessel endothelial cell line (HMEC-1). In contrast, H2O2 selectively induced only ICAM-1 in HMEC-1 and only IL-8 in A549. This cell type-specific pattern of IL-8 expression was also observed in several other endothelial and epithelial cells. TNFα induced greater IL-8 gene expression as compared with H2O2, but the kinetics of induction were similar. The induction of epithelial IL-8 message was accompanied by a corresponding increase in functional IL-8 protein secretion as determined by a neutrophil motility assay. The increased neutrophil motility stimulated by conditioned media from H2O2- or TNFα-exposed A549 cells was completely inhibited by an anti-IL-8 antibody. TNFα and H2O2 also induced a differential pattern of CC chemokine expression in A549. While TNFα induced both RANTES and MCP-1, H2O2 induced only MCP-1. These data suggest that epithelial cells under oxidant stress contribute to the inflammatory cytokine network by selective production of IL-8, MCP-1, and RANTES, which may critically influence the site-specific recruitment of leukocyte subsets.

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*

This work was in partial fulfillment of the requirements for a Ph.D (V. L.) and was supported in part by grants from the American Heart Association (to K. A. R. and R. H. C.), a grant from the American Cancer Society of Illinois (to K. A. R.), and United States Public Health Service Grant R01 GM43241-07 from the National Institute of General Medical Sciences, National Institutes of Health.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.

Established Investigator of the American Heart Association/Bristol-Myers Squibb.