Systemically administered ligands of toll-like receptor 2, -4, and -9 induce distinct inflammatory responses in the murine lung

Abstract

Objective. To determine whether systemically administered TLR ligands differentially modulate pulmonary inflammation. Methods. Equipotent doses of LPS (20mg/kg), CpG-ODN (1668-thioat 1nmol/g), or LTA (15mg/kg) were determined via TNF activity assay. C57BL/6 mice were challenged intraperitoneally. Pulmonary NFB activation (2h) and gene expression/activity of key inflammatory mediators (4h) were monitored. Results. All TLR ligands induced NFB. LPS increased the expression of TLR2, 6, and the cytokines IL-1, TNF-, IL-6, and IL-12p35/p40, CpG-ODN raised TLR6, TNF-, and IL12p40. LTA had no effect. Additionally, LPS increased the chemokines MIP-1/, 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. Copyright 2011 H. Ehrentraut et al.