Oxidant stress regulation of IL-8 and ICAM-1 gene expression: Differentialactivation and binding of the transcription factors AP-1 and NF-kappa B

Reactive oxygen species (ROS), generated either extracellularly or intracel lularly through ligand-receptor interactions, can function as signal transd uction molecules to activate the chemotactic cytokine interleukin-8 (IL-8) and the cell surface adhesion protein, intercellular adhesion molecule-1 (I CAM-1; CD54). Together, IL-8 and ICAM-1 orchestrate the transendothelial mi gration of neutrophils to sites of inflammation and injury. Recent results demonstrate that oxidant stress generated directly by exogenous H2O2 differ entially 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 epithelia l cell line, whereas in a microvessel endothelial cell line (HMEC-1) as wel l as in primary endothelial cells, H2O2 induces ICAM-1 but not IL-8, which is spontaneously expressed. In contrast, the proinflammatory cytokine TNF a lpha whose activity is dependent on the generation of intracellular ROS, in duces IL-8 and ICAM-1 in both cell types. The differential induction of IL- 8 and ICAM-1 by H2O2 and TNF alpha suggest that the two inflammatory stimul i target distinct redox responsive signaling pathways to activate cell type -specific gene expression. In this regard, we found that the cell type-spec ific pattern of IL-8 and ICAM-1 gene expression was associated with the dif ferential activation and promoter binding of the redox regulated transcript ion factors AP-1 and NF-KB. In this review, our current understanding of th e redox regulation of the IL-8 and ICAM-1 genes is summarized, and the diff erential roles AP-1 and NF-KB play in their cell type-specific expression, with particular emphasis on the differential effects induced by TNF alpha a nd H2O2, is discussed.