Fachbereich Veterinärmedizin


Service-Navigation

    Publikationsdatenbank

    Role of Pneumococcal Autolysin for KLF4 Expression and Chemokine Secretion in Lung Epithelium (2015)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Zahlten, Janine
    Herta, Toni
    Kabus, Christin
    Steinfeldt, Magdalena
    Kershaw, Olivia (WE 12)
    García, Pedro
    Hocke, Andreas C
    Gruber, Achim D (WE 12)
    Hübner, Ralf-Harto
    Steinicke, Robert
    Doehn, Jan-Moritz
    Suttorp, Norbert
    Hippenstiel, Stefan
    Quelle
    American journal of respiratory cell and molecular biology; 53(4) — S. 544–554
    ISSN: 1535-4989
    Sprache
    Englisch
    Verweise
    DOI: 10.1165/rcmb.2014-0024OC
    Pubmed: 25756955
    Kontakt
    Institut für Tierpathologie

    Robert-von-Ostertag-Str. 15
    Gebäude 12
    14163 Berlin
    Tel.+49 30 838 62450 Fax.+49 30 838 62522

    Abstract / Zusammenfassung

    In severe pneumococcal pneumonia, the delicate balance between a robust inflammatory response necessary to kill bacteria and the loss of organ function determines the outcome of disease. In this study, we tested the hypothesis that Krueppel-like factor (KLF) 4 may counter-regulate Streptococcus pneumoniae-related human lung epithelial cell activation using the potent proinflammatory chemokine IL-8 as a model molecule. Pneumococci induced KLF4 expression in human lung, in primary human bronchial epithelial cells, and in the lung epithelial cell line BEAS-2B. Whereas proinflammatory cell activation depends mainly on the classical Toll-like receptor 2-mitogen-activated protein kinase or phosphatidylinositide 3-kinase and NF-κB pathways, the induction of KLF4 occurred independently of these molecules but relied, in general, on tyrosine kinase activation and, in part, on the src kinase family member yamaguchi sarcoma viral oncogene homolog (yes) 1. The up-regulation of KLF4 depended on the activity of the main pneumococcal autolysin LytA. KLF4 overexpression suppressed S. pneumoniae-induced NF-κB and IL-8 reporter gene activation and release, whereas small interfering RNA-mediated silencing of KLF4 or yes1 kinase led to an increase in IL-8 release. The KLF4-dependent down-regulation of NF-κB luciferase activity could be rescued by the overexpression of the histone acetylase p300/cAMP response element-binding protein-associated factor. In conclusion, KLF4 acts as a counter-regulatory transcription factor in pneumococci-related proinflammatory activation of lung epithelial cells, thereby potentially preventing lung hyperinflammation and subsequent organ failure.