title: Expression of IL-6 and TNF-alpha in human alveolar epithelial cells is induced by invading, but not by adhering, Legionella pneumophila.
abstract: Legionella pnemophila causes atypical pneumonia in humans, especially in patients with chronic pulmonary diseases and underlying immunosuppression, and in elderly people. Several previous studies have shown that L. pneumophila induced several inflammatory cytokines in murine macrophages, but little is known about cytokine induction by the bacterium in lung epithelial cells. In this study, we investigated the ability of L. pneumophila to stimulate the production of pro-inflammatory cytokines in the human A549 alveolar epithelial cell line during 24h exposure to 10(6), 10(7), and 10(8) microbes. Infection of the wild L. pneumophila strain to A549 resulted in increased levels of interleukin-8 (IL-8), IL-6, and tumor necrosis factor alpha (TNF-alpha) mRNA, and also the secretion of their production into culture medium. In contrast, the level of mRNAs and proteins of IL-1beta and gamma interferon (IFN-gamma) remained unchanged and undetected, respectively. Production of IL-8, IL-6, and TNF-alpha in A549 decreased when an icmE multiplication-less mutant and the heat-killed L. pneumophila strain were inoculated. The treatment of cytochalasin D, which effectively inhibited invasion of L. pneumophila into A549, significantly reduced the production of IL-6 and TNF-alpha, but not IL-8. These results suggested that the induction and expression of IL-6 and TNF-alpha in the human alveolar epithelial cells especially required intracellular signaling by L. pneumophila after invasion.
authors.affiliation: Department of Bacteriology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Bin
authors.initials: B
authors.lastname: Chang
authors.forename: Junko
authors.initials: J
authors.lastname: Amemura-Maekawa
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Kura
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kawamura
authors.forename: Haruo
authors.initials: H
authors.lastname: Watanabe
mesh_terms: D001422:Bacterial Adhesion; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology*; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D016952:Legionella pneumophila / Q000472:pathogenicity* / Q000502:physiology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000276:immunology / Q000382:microbiology*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha