Toll-like receptor 7 activation reduces the contractile response of airway smooth muscle

Eur J Pharmacol. 2011 Feb 10;652(1-3):145-51. doi: 10.1016/j.ejphar.2010.11.009. Epub 2010 Nov 27.


Viral respiratory infections are a major cause of asthma exacerbations. The mechanisms by which such infections aggravate airway inflammation and hyperresponsiveness are complex and not fully understood. Toll-like receptor 7 is particularly relevant in the defence against common respiratory viruses, as it recognizes single-stranded viral RNA. The present study was designed to investigate the effect of Toll-like receptor 7 stimulation on airway smooth muscle reactivity. The presence of Toll-like receptor 7 within guinea pig airways was ensured with immunohistochemistry. The effects induced by 3days of culture of tracheal segments with the Toll-like receptor 7 agonist R837 or the Toll-like receptor 7/8 agonist R848 were evaluated in a myograph organ bath system. The intracellular mechanisms involved were dissected using inhibitors of intracellular mitogen-activated protein kinase (MAPK) activity. Toll-like receptor 7 immunoreactivity was observed across the epithelial cell layer and in the airway smooth muscle cells. Treatment with R837 and R848 reduced the airway contractile responses to 5-hydroxytryptamine (5-HT). This effect was abolished upon treatment with inhibitors of the p38 MAPK pathway and nuclear factor (NF)-κB pathways. According to the present model, activation of Toll-like receptor 7 might prevent development of airway hyperresponsiveness by acting on the airway smooth muscle. The presented data support the idea that individuals with defect Toll-like receptor 7 function might be more prone to respond to virus infections with asthmatic exacerbations. Further, they suggest that inhaled Toll-like receptor 7 ligand might be an effective treatment alternative for asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Female
  • Guinea Pigs
  • Hypersensitivity / drug therapy*
  • Hypersensitivity / metabolism
  • Hypersensitivity / pathology
  • Imidazoles / therapeutic use
  • MAP Kinase Kinase Kinases / metabolism
  • Muscle Contraction / drug effects*
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / metabolism
  • NF-kappa B / metabolism
  • Quinolines / therapeutic use*
  • Toll-Like Receptor 7 / agonists*
  • Toll-Like Receptor 7 / metabolism*
  • Trachea / drug effects*
  • Trachea / metabolism


  • 1-(2-methylpropyl)-1H-imidazo(4,5-c)quinolin 4-amine
  • Imidazoles
  • NF-kappa B
  • Quinolines
  • Toll-Like Receptor 7
  • MAP Kinase Kinase Kinases
  • resiquimod