Mechanisms of <it>Legionella pneumophila</it>-induced interleukin-8 expression in human lung epithelial cells

• Main Authors: Tomimori Koh, Okudaira Taeko, Ishikawa Chie, Akamine Morikazu, Higa Futoshi, Teruya Hiromitsu, Mukaida Naofumi, Tateyama Masao, Heuner Klaus, Fujita Jiro, Mori Naoki
• Format: Article
• Language: English
• Published: BMC 2007-11-01
• Series: BMC Microbiology
• Online Access: http://www.biomedcentral.com/1471-2180/7/102

<p>Abstract</p> <p>Background</p> <p><it>Legionella pneumophila </it>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 <it>L. pneumophila </it>on the expression of interleukin-8 (IL-8) in human A549 alveolar and NCI-H292 tracheal epithelial cell lines.</p> <p>Results</p> <p>Infection of <it>L. pneumophila </it>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 <it>L. pneumophila </it>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 <it>Legionella</it>. Activation of the IL-8 promoter by <it>L. pneumophila </it>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 <it>L. pneumophila</it>-mediated activation of IL-8 promoter. Treatment with hsp90 inhibitor suppressed <it>L. pneumophila</it>-induced IL-8 mRNA due to deactivation of NF-κB.</p> <p>Conclusion</p> <p>Collectively, these results suggest that <it>L. pneumophila </it>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 <it>L. pneumophila</it>-induced IL-8 expression, presumably contributing to immune response in <it>L. pneumophila</it>. The presence of flagellin and a type IV secretion system are critical for <it>Legionella </it>to induce IL-8 expression in lung epithelial cells.</p>