title: 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 (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.
  
  
  CONCLUSIONS
  Pulmonary susceptibility to systemic inflammation was highest after LPS, intermediate after CpG-ODN, and lowest after LTA challenge.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Ehrentraut
authors.forename: R
authors.initials: R
authors.lastname: Meyer
authors.forename: M
authors.initials: M
authors.lastname: Schwederski
authors.forename: S
authors.initials: S
authors.lastname: Ehrentraut
authors.forename: M
authors.initials: M
authors.lastname: Velten
authors.forename: C
authors.initials: C
authors.lastname: Grohé
authors.forename: P
authors.initials: P
authors.lastname: Knuefermann
authors.forename: G
authors.initials: G
authors.lastname: Baumgarten
authors.forename: O
authors.initials: O
authors.lastname: Boehm
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D008024:Ligands; D008168:Lung / Q000276:immunology* / Q000502:physiology; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D016207:Cytokines; D008024:Ligands; D019714:Tissue Inhibitor of Metalloproteinases; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; D020782:Matrix Metalloproteinases