Yersinia enterocolitica impairs activation of transcription factor NF-kappaB: involvement in the induction of programmed cell death and in the suppression of the macrophage tumor necrosis factor alpha production.

Abstract

In this study, we investigated the activity of transcription factor NF-kappaB in macrophages infected with Yersinia enterocolitica. Although triggering initially a weak NF-kappaB signal, Y. enterocolitica inhibited NF-kappaB activation in murine J774A.1 and peritoneal macrophages within 60 to 90 min. Simultaneously, Y. enterocolitica prevented prolonged degradation of the inhibitory proteins IkappaB-alpha and IkappaB-beta observed by treatment with lipopolysaccharide (LPS) or nonvirulent, plasmid-cured yersiniae. Analysis of different Y. enterocolitica mutants revealed a striking correlation between the abilities of these strains to inhibit NF-kappaB and to suppress the tumor necrosis factor alpha (TNF-alpha) production as well as to trigger macrophage apoptosis. When NF-kappaB activation was prevented by the proteasome inhibitor MG-132, nonvirulent yersiniae as well as LPS became able to trigger J774A.1 cell apoptosis and inhibition of the TNF-alpha secretion. Y. enterocolitica also impaired the activity of NF-kappaB in epithelial HeLa cells. Although neither Y. enterocolitica nor TNF-alpha could induce HeLa cell apoptosis alone, TNF-alpha provoked apoptosis when activation of NF-kappaB was inhibited by Yersinia infection or by the proteasome inhibitor MG-132. Together, these data demonstrate that Y. enterocolitica suppresses cellular activation of NF-kappaB, which inhibits TNF-alpha release and triggers apoptosis in macrophages. Our results also suggest that Yersinia infection confers susceptibility to programmed cell death to other cell types, provided that the appropriate death signal is delivered.

• Authors: K Ruckdeschel, S Harb, A Roggenkamp, M Hornef, R Zumbihl, S Köhler, J Heesemann, B Rouot
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 187 Issue 7 Pg. 1069-79 (Apr 06 1998) ISSN: 0022-1007 [Print] United States
• PMID: 9529323 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• Enzyme Inhibitors
• Flavonoids
• Imidazoles
• Leupeptins
• Lipopolysaccharides
• NF-kappa B
• Pyridines
• Tumor Necrosis Factor-alpha
• SB 203580
• benzyloxycarbonylleucyl-leucyl-leucine aldehyde
• 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Topics

• Animals
• Apoptosis (physiology)
• Cell Line
• DNA-Binding Proteins (metabolism)
• Enzyme Inhibitors (pharmacology)
• Flavonoids (pharmacology)
• Gene Expression Regulation (genetics)
• Humans
• Imidazoles (pharmacology)
• Leupeptins (pharmacology)
• Lipopolysaccharides (pharmacology)
• Macrophages, Peritoneal (microbiology)
• Mice
• NF-kappa B (metabolism)
• Pyridines (pharmacology)
• Serotyping
• Suppression, Genetic (genetics)
• Transcriptional Activation (genetics)
• Tumor Necrosis Factor-alpha (metabolism)
• Yersinia enterocolitica (genetics, pathogenicity)