title: CpG oligonucleotide activates Toll-like receptor 9 and causes lung inflammation in vivo.
abstract: BACKGROUND
  Bacterial 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.
  
  
  METHODS
  Wild-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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  This study suggests that bacterial CpG-ODN causes lung inflammation via TLR9.
authors.affiliation: Department for Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53125 Bonn, Germany. pascal.knuefermann@ukb.uni-bonn.de
authors.forename: Pascal
authors.initials: P
authors.lastname: Knuefermann
authors.forename: Georg
authors.initials: G
authors.lastname: Baumgarten
authors.forename: Alexander
authors.initials: A
authors.lastname: Koch
authors.forename: Markus
authors.initials: M
authors.lastname: Schwederski
authors.forename: Markus
authors.initials: M
authors.lastname: Velten
authors.forename: Heidi
authors.initials: H
authors.lastname: Ehrentraut
authors.forename: Jan
authors.initials: J
authors.lastname: Mersmann
authors.forename: Rainer
authors.initials: R
authors.lastname: Meyer
authors.forename: Andreas
authors.initials: A
authors.lastname: Hoeft
authors.forename: Kai
authors.initials: K
authors.lastname: Zacharowski
authors.forename: Christian
authors.initials: C
authors.lastname: Grohé
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D004269:DNA, Bacterial; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007958:Leukocyte Count; D008168:Lung / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D009838:Oligodeoxyribonucleotides; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000097:blood / Q000139:chemically induced / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013997:Time Factors; D051217:Toll-Like Receptor 9 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C408982:CPG-oligonucleotide; D016207:Cytokines; D004269:DNA, Bacterial; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase