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DOI: 10.1055/s-2006-932726
Pneumococci induced IL-8 expression in human pulmonary epithelium by TLR1 and TLR2 and Rac1
Introduction: 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 and Rho-GTPase signaling in the activation of human lung epithelial cells by pneumococci.
Methods: BEAS-2B cells, transient transfection, IL-8 ELISA, chromatin-immunoprcipitation.
Results: S. pneumoniae induced release of IL-8 by human bronchial epithelial cell line BEAS-2B. Specific inhibition of Rac1 by Nsc23766 or dominant-negative mutants of Rac1 strongly reduced cytokine release. In addition, pneumococci-related cell activation (IL-8 release, NF-kB-activation) depended on Cdc42, phosphatidylinositol 3-kinase and MyD88 but not on RhoA. Pneumococci enhanced TLR1 and TLR2 mRNA-expression in BEAS-2B cells, while TLR4 and TLR 6-expression was constitutively high. TLR1 and 2 synergistically recognized pneumococci in co-transfection experiments. TLR4, TLR6, LBP, and CD14 seem not to be involved in pneumococci-dependent cell activation. At the IL-8 gene promoter, recruitment of phosphorylated NF-kB-subunit p65 was blocked by inhibition of Rac1, whereas binding of the phosphorylated AP-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 Pi3K- and Rac1-dependent NF-κB-recruitment to the IL-8 promoter.
The German Federal Ministry of Education and Research, Competence Network CAPNETZ supported this study.