• Pascal Knuefermann, Georg Baumgarten, Alexander Koch, Markus Schwederski, Markus Velten, Heidi Ehrentraut, Jan Mersmann, Rainer Meyer, Andreas Hoeft, Kai Zacharowski, and Christian Grohé.
• Department for Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53125 Bonn, Germany. pascal.knuefermann@ukb.uni-bonn.de
• Resp Res. 2007 Jan 1;8:72.

BackgroundBacterial DNA containing motifs of unmethylated CpG dinucleotides (CpG-ODN) initiate an innate immune response mediated by the pattern recognition receptor Toll-like receptor 9 (TLR9). This leads in particular to the expression of proinflammatory mediators such as tumor necrosis factor (TNF-alpha) and interleukin-1beta (IL-1beta). TLR9 is expressed in human and murine pulmonary tissue and induction of proinflammatory mediators has been linked to the development of acute lung injury. Therefore, the hypothesis was tested whether CpG-ODN administration induces an inflammatory response in the lung via TLR9 in vivo.MethodsWild-type (WT) and TLR9-deficient (TLR9-D) mice received CpG-ODN intraperitoneally (1668-Thioat, 1 nmol/g BW) and were observed for up to 6 hrs. Lung tissue and plasma samples were taken and various inflammatory markers were measured.ResultsIn WT mice, CpG-ODN induced a strong activation of pulmonary NFkappaB as well as a significant increase in pulmonary TNF-alpha and IL-1beta mRNA/protein. In addition, cytokine serum levels were significantly elevated in WT mice. Increased pulmonary content of lung myeloperoxidase (MPO) was documented in WT mice following application of CpG-ODN. Bronchoalveolar lavage (BAL) revealed that CpG-ODN stimulation significantly increased total cell number as well as neutrophil count in WT animals. In contrast, the CpG-ODN-induced inflammatory response was abolished in TLR9-D mice.ConclusionThis study suggests that bacterial CpG-ODN causes lung inflammation via TLR9.

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