Pneumococci induced TLR- and Rac1-dependent NF-kappaB-recruitment to the IL-8 promoter in lung epithelial cells

Bernd Schmeck, Sylvia Huber, Kerstin Moog, Janine Zahlten, Andreas C Hocke, Bastian Opitz, Sven Hammerschmidt, Tim J Mitchell, Michael Kracht, Simone Rosseau, Norbert Suttorp, Stefan Hippenstiel

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69 Citations (Scopus)


Streptococcus pneumoniae is the major pathogen of community-acquired pneumonia. The respiratory epithelium constitutes the first line of defense against invading lung pathogens, including pneumococci. We analyzed the involvement of Toll-like receptors (TLR) and Rho-GTPase signaling in the activation of human lung epithelial cells by pneumococci. S. pneumoniae induced release of interleukin-8 (IL-8) by human bronchial epithelial cell line BEAS-2B. Specific inhibition of Rac1 by Nsc23766 or a dominant-negative mutant of Rac1 strongly reduced cytokine release. In addition, pneumococci-related cell activation (IL-8 release, NF-kappaB-activation) depended on MyD88, phosphatidylinositol 3-kinase, and Cdc42 but not on RhoA. Pneumococci enhanced TLR1 and TLR2 mRNA expression in BEAS-2B cells, whereas TLR4 and TLR6 expression was constitutively high. TLR1 and 2 synergistically recognized pneumococci in cotransfection experiments. TLR4, TLR6, LPS-binding protein, and CD14 seem not to be involved in pneumococci-dependent cell activation. At the IL-8 gene promoter, recruitment of phosphorylated NF-kappaB subunit p65 was blocked by inhibition of Rac1, whereas binding of the phosphorylated activator protein-1 subunit c-Jun to the promoter was not diminished. In summary, these results suggest that S. pneumoniae activate human epithelial cells by TLR1/2 and a phosphatidylinositol 3-kinase- and Rac1-dependent NF-kappaB-recruitment to the IL-8 promoter.
Original languageEnglish
Pages (from-to)L730-L737
JournalAmerican journal of physiology. Lung cellular and molecular physiology
Issue number4
Publication statusPublished - Apr 2006


  • Adaptor Proteins, Signal Transducing
  • Bacterial Outer Membrane Proteins
  • Bacterial Proteins
  • Bronchi
  • Cell Line
  • Epithelial Cells
  • Humans
  • Interleukin-8
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • Phosphatidylinositol 3-Kinases
  • Phosphorylation
  • Promoter Regions, Genetic
  • Signal Transduction
  • Streptococcus pneumoniae
  • Streptolysins
  • Toll-Like Receptor 1
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Transcription Factor RelA
  • Transcription, Genetic
  • rac1 GTP-Binding Protein
  • rho GTP-Binding Proteins


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