Consequences of chronic pulmonary TLR9 activation in the lung and beyond

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Abstract

Background: Toll like receptor 9 (TLR9) agonist CpG-ODN is being explored as an anti-allergic drug for asthma. However TLR9 could play a role in COPD. Cigarette smoke induced IL-8 production is partly TLR9 mediated. Aim: To investigate the (extra)-pulmonary effects of CpG-ODN. We hypothesized that pulmonary TLR9 activation induces neutrophil influx which could lead to adverse effects. Methods: A single dose of 0.01, 0.05 or 0.25nMol/gBW GpGODN was targeted to balb/c mice lungs by aspiration (acute). Next 0.01nMol/gBW GpGODN was administered repeatedly for 5 days (subchronic) or 5 weeks (chronic). 24 hours after last exposures, measurements were done: lung function; hypertension and heart hypertrophy; lung weight; blood and bronchoalveolar lavage (BAL) analysis; morphology of unlavaged lungs. Results: Total BAL cells were increased in all CpG-ODN mice (p
Original languageEnglish
Publication statusPublished - 1 Sept 2011

Keywords

  • CpG oligodeoxynucleotide
  • toll like receptor 9
  • cigarette smoke
  • interleukin 8
  • European
  • society
  • lung
  • lymphocyte
  • long term exposure
  • lung weight
  • neutrophil
  • heart hypertrophy
  • heart right ventricle
  • blood
  • aspiration
  • Bagg albino mouse
  • heart weight
  • exposure
  • hypertension
  • single drug dose
  • agonist
  • adverse drug reaction
  • asthma
  • mouse
  • morphology
  • lung lavage
  • peak expiratory flow
  • airway resistance
  • cardiovascular effect
  • lung function

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