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Mechanisms of Legionella pneumophila-induced interleukin-8 expression in human lung epithelial cells.
- Source :
-
BMC microbiology [BMC Microbiol] 2007 Nov 22; Vol. 7, pp. 102. Date of Electronic Publication: 2007 Nov 22. - Publication Year :
- 2007
-
Abstract
- Background: Legionella pneumophila is a facultative intracellular bacterium, capable of replicating within the phagosomes of macrophages and monocytes, but little is known about its interaction with human lung epithelial cells. We investigated the effect of L. pneumophila on the expression of interleukin-8 (IL-8) in human A549 alveolar and NCI-H292 tracheal epithelial cell lines.<br />Results: Infection of L. pneumophila strain, but not heat-killed strain, resulted in upregulation of IL-8. IL-8 mRNA expression was induced immediately after the infection and its signal became gradually stronger until 24 h after infection. On the other hand, IL-8 expression in A549 cells infected with L. pneumophila lacking a functional type IV secretion system was transient. The IL-8 expression was slightly induced at 16 h and increased at 24 h after infection with flagellin-deficient Legionella. Activation of the IL-8 promoter by L. pneumophila infection occurred through the action of nuclear factor-kappaB (NF-kappaB). Transfection of dominant negative mutants of NF-kappaB-inducing kinase, IkappaB kinase and IkappaB inhibited L. pneumophila-mediated activation of IL-8 promoter. Treatment with hsp90 inhibitor suppressed L. pneumophila-induced IL-8 mRNA due to deactivation of NF-kappaB.<br />Conclusion: Collectively, these results suggest that L. pneumophila induces activation of NF-kappaB through an intracellular signaling pathway that involves NF-kappaB-inducing kinase and IkappaB kinase, leading to IL-8 gene transcription, and that hsp90 acts as a crucial regulator in L. pneumophila-induced IL-8 expression, presumably contributing to immune response in L. pneumophila. The presence of flagellin and a type IV secretion system are critical for Legionella to induce IL-8 expression in lung epithelial cells.
- Subjects :
- Benzoquinones pharmacology
Cell Line, Tumor
Electrophoretic Mobility Shift Assay
Epithelial Cells metabolism
Epithelial Cells microbiology
Gene Expression Regulation
HSP90 Heat-Shock Proteins antagonists & inhibitors
Humans
Lactams, Macrocyclic pharmacology
Legionella pneumophila growth & development
Lung metabolism
Lung microbiology
NF-kappa B metabolism
Phosphorylation
Promoter Regions, Genetic
Protein Serine-Threonine Kinases metabolism
Transcription, Genetic
Transfection
NF-kappaB-Inducing Kinase
Epithelial Cells immunology
Interleukin-8 genetics
Interleukin-8 immunology
Legionella pneumophila immunology
Lung immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1471-2180
- Volume :
- 7
- Database :
- MEDLINE
- Journal :
- BMC microbiology
- Publication Type :
- Academic Journal
- Accession number :
- 18034886
- Full Text :
- https://doi.org/10.1186/1471-2180-7-102