Pneumologie 2013; 67 - V244
DOI: 10.1055/s-0033-1334525

Krueppel-like Factor 4 terminates Streptococcus pneumonia-dependent IL-8 release and induces IL-10 expression in human Lung Epithelial Cells

J Zahlten 1, R Steinicke 1, W Bertrams 2, AC Hocke 3, B Schmeck 2, M Witzenrath 1, N Suttorp 1, S Hippenstiel 4
  • 1Charité-Universitätsmedizin Berlin, II. Medizinische Klinik m.S. Infektiologie und Pneumologie
  • 2Molecular Pulmonology, Universities of Gießen and Marburg Lung Center, German Center for Lung Research, Philipps University, Marburg
  • 3Med. Klinik m.S. Infektiologie und Pneumologie Charité-Universitätsmedizin Berlin Forschungslabor Ccm, Berlin
  • 4Charité Universitätsmedizin, Campus Virchow, Klinikum Medizinische Klinik Sp Infektiologie, Berlin

Objective: Streptococcus pneumoniae is the most common cause of community-acquired pneumonia throughout the world. The release of potent pro-inflammatory mediators is not only central for mounting an efficient host response, it always bears the risk of deleterious excessive tissue damaging inflammation. This is highlighted in severe pneumococcal pneumonia, in which the delicate balance among a robust inflammatory response to kill pneumococci and loss of organ function determines outcome of disease.

The aim of this study was to clarify the role of Krueppel-like factor 4 (KLF4) in pneumococcal pneumonia especially with regard to pro- and anti-inflammatory cytokine release.

Methods: small airway epithelial cells (SAEC); human broncho-epithelial cell line (BEAS-2B); human embryonic kidney cell line (HEK293); S. pneumoniae strains R6x as well as a pneumolysin negative mutant; R6x- and CpG- (ODN M362) DNA

Western-blot; ELISA; reporter gen assay, ChIP; chemical Inhibitors (PP2; PP3; ODN TTAGGG); siRNA

Results: We could show that pneumococci-induced TLR9- and src kinase-dependent the expression of KLF4 in lung epithelial cells thereby causing an abolishment of pro-inflammatory IL-8 release and the induction of anti-inflammatory IL-10.

Conclusion: Bacterial DNA-related TLR9-src kinase activation induced KLF4 expression initiating expression of anti-inflammatory mediators like IL-10 and a termination of pro-inflammatory IL-8. Thus, besides activating the innate immune response, untypical TLR-related signalling pathways may be important to control the inflammatory response in severe infections preventing deleterious tissue damaging.