Abstract
IL‐8 is an inflammatory CXC chemokine involved in neutrophil recruitment and activation in various inflammatory conditions. The transcriptional profile induced by IL‐8 in human neutrophils wasanalyzed using high‐density oligonucleotide arrays and compared with that of the prototypic phagocyte activator LPS. As expected, LPS induced a major effect on the cell transcriptome, upregulating 116 (0.93%) and downregulating 70 (0.56%) of the transcripts. IL‐8 induced a less profound modulation of the cell transcriptome, with upregulation of 30 (0.25%) and downregulation of 6 (0.04%) of the transcripts. Although the two proinflammatory mediators induced partially overlapping transcriptional profiles (50.0% of IL‐8‐responsive genes were concordantly regulated by LPS), IL‐8 also modulated a significant number of genes unresponsive to LPS, including soluble mediators, membrane receptors, signaling molecules, and regulators of transcription and translation. A set of IL‐8‐inducible genes was related to cell motility, possibly a strategy to prepare for migration into tissues. Analysis of the IL‐8‐responsive gene IL‐1β at the protein level revealed that transcript induction was not followed by protein production. Neutrophils stimulated with IL‐8, however, showed a significant increase in IL‐1β secretion after subsequent exposure to LPS. Thus, the effect of IL‐8 at the transcriptional level could provide a synergistic effect with microbial products for neutrophil activation.