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Review
, 4 (3), 223-30

Oxidant Stress Regulation of IL-8 and ICAM-1 Gene Expression: Differential Activation and Binding of the Transcription Factors AP-1 and NF-kappaB (Review)

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Review

Oxidant Stress Regulation of IL-8 and ICAM-1 Gene Expression: Differential Activation and Binding of the Transcription Factors AP-1 and NF-kappaB (Review)

K A Roebuck. Int J Mol Med.

Abstract

Reactive oxygen species (ROS), generated either extracellularly or intracellularly through ligand-receptor interactions, can function as signal transduction molecules to activate the chemotactic cytokine interleukin-8 (IL-8) and the cell surface adhesion protein, intercellular adhesion molecule-1 (ICAM-1; CD54). Together, IL-8 and ICAM-1 orchestrate the transendothelial migration of neutrophils to sites of inflammation and injury. Recent results demonstrate that oxidant stress generated directly by exogenous H2O2 differentially induce IL-8 and ICAM-1 transcription in epithelial and endothelial cells. H2O2 induces IL-8 but not ICAM-1 in the A549 type-II-like epithelial cell line, whereas in a microvessel endothelial cell line (HMEC-1) as well as in primary endothelial cells, H2O2 induces ICAM-1 but not IL-8, which is spontaneously expressed. In contrast, the pro-inflammatory cytokine TNFalpha, whose activity is dependent on the generation of intracellular ROS, induces IL-8 and ICAM-1 in both cell types. The differential induction of IL-8 and ICAM-1 by H2O2 and TNFalpha suggest that the two inflammatory stimuli target distinct redox responsive signaling pathways to activate cell type-specific gene expression. In this regard, we found that the cell type-specific pattern of IL-8 and ICAM-1 gene expression was associated with the differential activation and promoter binding of the redox regulated transcription factors AP-1 and NF-kappaB. In this review, our current understanding of the redox regulation of the IL-8 and ICAM-1 genes is summarized, and the differential roles AP-1 and NF-kappaB play in their cell type-specific expression, with particular emphasis on the differential effects induced by TNFalpha and H2O2 is discussed.

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