title: Involvement of epidermal growth factor receptor-linked signaling responses in Pseudomonas fluorescens-infected alveolar epithelial cells.
abstract: Pseudomonas fluorescens is an opportunistic indoor pathogen that can cause severe airway proinflammatory responses. Pulmonary epithelium, like other mucosal epithelial linings of the body, constitutes the first line of defense against airway microbial pathogens. Mucosal epithelial cells can be a sentinel of pathogenic bacteria via stimulation of specific cell surface receptors, including the epidermal growth factor receptor (EGFR) and Toll-like receptor (TLR). This study addressed the involvement of EGFR in airway epithelial pathogenesis by P. fluorescens. Human A549 pneumocytes showed prolonged production of proinflammatory interleukin-8 (IL-8) in response to infection with P. fluorescens, which was via the nuclear factor-kappa B (NF-κB) signaling pathway. Production of proinflammatory cytokine IL-8 was not mediated by P. fluorescens lipopolysaccharide, a representative TLR4 agonist, but was mediated through EGFR-linked signals activated by the opportunistic bacteria. Moreover, EGFR signals were involved in NF-κB signal-mediated production of proinflammatory cytokines. Along with persistent NF-κB activation, P. fluorescens enhanced the EGFR phosphorylation and subsequent activation of downstream mediators, including protein kinase B or extracellular-signal-regulated kinases 1/2. Blocking of EGFR-linked signals increased epithelial susceptibility to pathogen-induced epithelial cell death, suggesting protective roles of EGFR signals. Thus, airway epithelial exposure to P. fluorescens can trigger antiapoptotic responses via EGFR and proinflammatory responses via TLR4-independent NF-κB signaling pathway in human pneumocytes.
authors.affiliation: Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan 626-813, South Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Choi
authors.forename: Chan Hee
authors.initials: CH
authors.lastname: Seo
authors.forename: Seong Hwan
authors.initials: SH
authors.lastname: Park
authors.forename: Hyun
authors.initials: H
authors.lastname: Yang
authors.forename: Kee Hun
authors.initials: KH
authors.lastname: Do
authors.forename: Juil
authors.initials: J
authors.lastname: Kim
authors.forename: Hyung-Kab
authors.initials: HK
authors.lastname: Kim
authors.forename: Duk-Hwa
authors.initials: DH
authors.lastname: Chung
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Ahn
authors.forename: Yuseok
authors.initials: Y
authors.lastname: Moon
mesh_terms: D017209:Apoptosis / Q000276:immunology; D015153:Blotting, Western; D002460:Cell Line; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D066246:ErbB Receptors / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D047468:Immunoprecipitation; D016209:Interleukin-8 / Q000096:biosynthesis / Q000276:immunology; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D011552:Pseudomonas Infections / Q000276:immunology* / Q000378:metabolism; D011551:Pseudomonas fluorescens / Q000276:immunology; D011650:Pulmonary Alveoli / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D016209:Interleukin-8; D016328:NF-kappa B; D066246:ErbB Receptors