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Mediators of Inflammation
Volume 2011, Article ID 746532, 12 pages
Research Article

Systemically Administered Ligands of Toll-Like Receptor 2, -4, and -9 Induce Distinct Inflammatory Responses in the Murine Lung

1Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany
2Institute of Physiology II, University of Bonn, Nussallee 11, 53115 Bonn, Germany
3Department for Pneumology, Evangelische Lungenklinik, Berlin, Lindenberger Weg 27, Haus 205, 13125 Berlin, Germany

Received 9 September 2010; Revised 12 January 2011; Accepted 23 January 2011

Academic Editor: Tânia Silvia Fröde

Copyright © 2011 H. Ehrentraut et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Objective. To determine whether systemically administered TLR ligands differentially modulate pulmonary inflammation. Methods. Equipotent doses of LPS (20 mg/kg), CpG-ODN (1668-thioat 1 nmol/g), or LTA (15 mg/kg) were determined via TNF activity assay. C57BL/6 mice were challenged intraperitoneally. Pulmonary NFκB activation (2 h) and gene expression/activity of key inflammatory mediators (4 h) were monitored. Results. All TLR ligands induced NFκB. LPS increased the expression of TLR2, 6, and the cytokines IL-1αβ, TNF-α, IL-6, and IL-12p35/p40, CpG-ODN raised TLR6, TNF-α, and IL12p40. LTA had no effect. Additionally, LPS increased the chemokines MIP-1α/β, MIP-2, TCA-3, eotaxin, and IP-10, while CpG-ODN and LTA did not. Myeloperoxidase activity was highest after LPS stimulation. MMP1, 3, 8, and 9 were upregulated by LPS, MMP2, 8 by CpG-ODN and MMP2 and 9 by LTA. TIMPs were induced only by LPS. MMP-2/-9 induction correlated with their zymographic activities. Conclusion. Pulmonary susceptibility to systemic inflammation was highest after LPS, intermediate after CpG-ODN, and lowest after LTA challenge.