Effect of an inhibitor of Jun N-terminal protein kinase, SP600125, in single allergen challenge in sensitized rats

Immunology. 2004 Jul;112(3):446-53. doi: 10.1111/j.1365-2567.2004.01887.x.


Jun N-terminal kinase (JNK) has been implicated in the pathogenesis of inflammatory diseases including asthma. We examined the effect of SP600125 (anthra [1,9-cd] pyrazol-6 (2H)-one), a novel inhibitor of JNK in a model of asthma. Brown-Norway rats were sensitized to ovalbumin and treated with SP600125 intraperitoneally (90 mg/kg in total). SP600125 inhibited allergen-induced, increased activity of phosphorylated c-jun but not of phosphorylated-MAPKAPK2, indicative of activation of p38 MAPK, in the lung. SP600125 inhibited macrophage (P < 0.04), lymphocyte (P < 0.05), eosinophil (P < 0.04) and neutrophil (P < 0.005) numbers in bronchoalveolar lavage. Eosinophil and T-cell accumulation in the airways, mRNA expression for interleukin-1beta, tumour necrosis factor-beta, interleukin-3, interleukin-4 and interleukin-5, serum levels of allergen-specific immunoglobulin E and bronchial hyperresponsiveness were not affected by SP600125. Selective inhibition of JNK reduced inflammatory cell egress into the airway lumen after single allergen exposure. The role of JNK mitogen-activated protein kinase activation may be limited in the pathogenesis of bronchial hyperresponsiveness after single allergen exposure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / pharmacology*
  • Animals
  • Anthracenes / pharmacology*
  • Asthma / immunology*
  • Bronchoalveolar Lavage Fluid / immunology
  • Cell Count
  • Cytokines / immunology
  • Enzyme Activation
  • Eosinophils / immunology
  • JNK Mitogen-Activated Protein Kinases*
  • Leukocyte Count
  • Leukocytes, Mononuclear / immunology
  • Lung / enzymology
  • Lung / immunology*
  • MAP Kinase Kinase 4
  • Macrophages / immunology
  • Male
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Mitogen-Activated Protein Kinases / metabolism
  • Models, Animal
  • Neutrophils / immunology
  • Ovalbumin
  • Rats
  • Rats, Inbred BN
  • p38 Mitogen-Activated Protein Kinases


  • Allergens
  • Anthracenes
  • Cytokines
  • pyrazolanthrone
  • Ovalbumin
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases