Invasive Shigella flexneri activates NF-kappa B through a lipopolysaccharide-dependent innate intracellular response and leads to IL-8 expression in epithelial cells

The pathogenesis of Shigella flexneri infection centers on the ability of t his organism to invade epithelial cells and initiate an intense inflammator y reaction. Because NF-kappa B is an important transcriptional regulator of genes involved in inflammation, we investigated the role of this transcrip tion factor during S, flexneri infection of epithelial cells. Infection of HeLa cells with invasive S. flexneri induced NF-kappa B DNA-binding activit y; noninvasive S. flexneri strains did not lead to this activation. The pat hway leading to NF-kappa B activation by invasive S. flexneri involved the kinases, NF-kappa B-inducing kinase, I kappa B kinase-l, and I kappa B kina se-2, NF-kappa B activation was linked to inflammation, because invasive S, flexneri activated an IL-8 promoter-driven reporter gene, and the kappa B site within this promoter was indispensable for its induction. Microinjecti on of bacterial culture supernatants into HeLa cells suggested that LPS is responsible for NF-kappa B activation by S, flexneri infection. In conclusi on, the eukaryotic transcription factor NF-kappa B was activated during S. flexneri infection of epithelial cells, which suggests a role for this tran scriptional regulator in modulating the immune response during infection in vivo.