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Mechanisms of Legionella pneumophila-induced interleukin-8 expression in human lung epithelial cells

Authors :
Tomimori Koh
Okudaira Taeko
Ishikawa Chie
Akamine Morikazu
Higa Futoshi
Teruya Hiromitsu
Mukaida Naofumi
Tateyama Masao
Heuner Klaus
Fujita Jiro
Mori Naoki
Source :
BMC Microbiology, Vol 7, Iss 1, p 102 (2007)
Publication Year :
2007
Publisher :
BMC, 2007.

Abstract

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. 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-κB (NF-κB). Transfection of dominant negative mutants of NF-κB-inducing kinase, IκB kinase and IκB 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-κB. Conclusion Collectively, these results suggest that L. pneumophila induces activation of NF-κB through an intracellular signaling pathway that involves NF-κB-inducing kinase and IκB 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

Subjects :
Microbiology
QR1-502

Details

Language :
English
ISSN :
14712180
Volume :
7
Issue :
1
Database :
Directory of Open Access Journals
Journal :
BMC Microbiology
Publication Type :
Academic Journal
Accession number :
edsdoj.2ab1c067e104f2aa67a54952740909e
Document Type :
article
Full Text :
https://doi.org/10.1186/1471-2180-7-102