Wortmannin blocks Yersinia invasin-triggered internalization, but not interleukin-8 production by epithelial cells

• Published in: Medical microbiology and immunology 1998-06, Vol.187 (1), p.53-60
• Main Authors: SCHULTE, R, ZUMBIHL, R, KAMPIK, D, FAUCONNIER, A, AUTENRIETH, I. B
• Format: Article
• Language: English
• Subjects: Adhesins, Bacterial; Androstadienes - pharmacology; Bacterial Adhesion - drug effects; Bacterial Outer Membrane Proteins - physiology; Bacterial Proteins - physiology; Bacteriology; Biological and medical sciences; Caco-2 Cells; Enzyme Inhibitors - pharmacology; Enzyme-Linked Immunosorbent Assay; Fundamental and applied biological sciences. Psychology; Genistein - pharmacology; HeLa Cells - drug effects; Humans; Interleukin-8 - genetics; Interleukin-8 - secretion; Microbiology; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Polymerase Chain Reaction; Staurosporine - pharmacology; Transcriptional Activation; Tumor Cells, Cultured; Yersinia enterocolitica; Yersinia enterocolitica - drug effects; Yersinia enterocolitica - enzymology; Yersinia enterocolitica - physiology
• ISSN: 0300-8584; 1432-1831
• DOI: 10.1007/s004300050074

In response to bacterial infection epithelial cells up-regulate expression and secretion of proinflammatory cytokines. Previous work from our laboratory showed that basolateral infection of polarized T84 cells with Yersinia enterocolitica induces interleukin-8 (IL-8) secretion in the absence of significant invasion. Here we studied Y. enterocolitica-induced IL-8 secretion by epithelial HeLa cells as a function of Yersinia invasion or adhesion. For this purpose we tried to separated induction of IL-8 secretion from invasion by treating HeLa cells with signal transduction inhibitors prior to infection. While staurosporin and genistein inhibited both Yersinia invasion and Yersinia-triggered IL-8 secretion, wortmannin, an inhibitor of the phosphatidylinositol-3-phosphate kinase (PI3-K), blocked invasion of Y. enterocolitica into HeLa cells but did not show any effect on IL-8 secretion. These results suggest that Yersinia adhesion might be sufficient to induce IL-8 secretion by epithelial cells. Further analysis demonstrated the requirement of the Yersinia invasion locus inv for adhesion-mediated induction of IL-8 secretion. Thus, HeLa cells infected with an E. coli strain expressing the Y. enterocolitica inv locus induced IL-8 secretion in the presence and absence of wortmannin. Reverse transcription-polymerase chain reaction analysis revealed that adhesion of inv-expressing Y. enterocolitica or E. coli results in the transcriptional activation of the IL-8 gene. These results suggest that Y. enterocolitica adhesion to host cells via Inv activates de novo synthesis and secretion of IL-8.