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PMID: 15196213 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Immunology ·Vol. 112 ·No. 3 ·2004-07-00 ·Pages 446-53

Eynott PR, Xu L, Bennett BL, Noble A, Leung SY, Nath P, Groneberg DA, Adcock IM, Chung KF

Abstract

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.

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,immunology MAP Kinase Kinase 4 Macrophages/immunology Male Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors,metabolism Mitogen-Activated Protein Kinases/metabolism Models, Animal Neutrophils/immunology Ovalbumin Rats Rats, Inbred BN p38 Mitogen-Activated Protein Kinases
Chemicals
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
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Eynott Paul R
Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, UK.
Xu Li
Bennett Brydon L
Noble Alistair
Leung Sum-Yee
Nath Puneeta
Groneberg David A
Adcock Ian M
Chung K Fan
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Article Info
Journal
Immunology
Abbr.
Immunology
ISSN
0019-2805
DOI
10.1111/j.1365-2567.2004.01887.x
Published
2004-07-00
Pages
446-53
Language
English
Region
England
NLM ID
0374672
PMCID
PMC1782503
Subset
IM
External Links
PubMed source DOI: 10.1111/j.1365-2567.2004.01887.x PMC Full Text View journal details
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