Allergen-induced inflammation and airway epithelial and smooth muscle cell proliferation: role of Jun N-terminal kinase

Br J Pharmacol. 2003 Dec;140(8):1373-80. doi: 10.1038/sj.bjp.0705569. Epub 2003 Nov 17.


Chronic cellular inflammation and airway wall remodelling with subepithelial fibrosis and airway smooth muscle (ASM) cell hyperplasia are features of chronic asthma. Jun N-terminal kinase (JNK) may be implicated in these processes by regulating the transcriptional activity of activator protein (AP)-1. We examined the effects of an inhibitor of JNK, SP600125 (anthra [1,9-cd] pyrazole-6 (2 H)-one), in a model of chronic allergic inflammation in the rat. Rats sensitised to ovalbumin (OA) were exposed to OA-aerosol every third day on six occasions and were treated with SP600125 (30 mg kg-1 b.i.d; 360 mg in total) for 12 days, starting after the second through to the sixth OA exposure. We measured eosinophilic and T-cell inflammation in the airways, proliferation of ASM cells and epithelial cells by incorporation of bromodeoxyuridine (BrdU), and bronchial responsiveness to acetylcholine. SP600125 significantly reduced the number of eosinophils (P<0.05) and lymphocytes (P<0.05) in bronchoalveolar lavage fluid, suppressed eosinophilic (P<0.05) and CD2+ T-cell (P<0.05) infiltration within the bronchial submucosa, and the increased DNA incorporation in ASM (P<0.05) and epithelial cell incorporation (P<0.05). SP600125 did not alter bronchial hyper-responsiveness observed after chronic allergen exposure. Pathways regulated by JNK positively regulate ASM cell proliferation and allergic cellular inflammation following chronic allergen exposure.

MeSH terms

  • Actins / metabolism
  • Animals
  • Anthracenes / pharmacology
  • Bronchi / drug effects
  • Bronchi / immunology
  • Bronchi / pathology
  • Bronchoalveolar Lavage Fluid / chemistry
  • Cell Count
  • Cell Division / drug effects
  • Chronic Disease
  • Eosinophils / drug effects
  • Eosinophils / pathology
  • Hypersensitivity / enzymology
  • Hypersensitivity / immunology
  • Hypersensitivity / pathology*
  • Immunohistochemistry
  • Inflammation / enzymology
  • Inflammation / immunology
  • Inflammation / pathology
  • JNK Mitogen-Activated Protein Kinases
  • Male
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / biosynthesis*
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / immunology
  • Myocytes, Smooth Muscle / pathology*
  • Ovalbumin / immunology
  • Rats
  • Rats, Inbred BN
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / metabolism*


  • Actins
  • Anthracenes
  • pyrazolanthrone
  • Ovalbumin
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases