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

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)‐...

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Veröffentlicht in:British journal of pharmacology 2003-12, Vol.140 (8), p.1373-1380
Hauptverfasser: Eynott, Paul R, Nath, Puneeta, Leung, Sum‐Yee, Adcock, Ian M, Bennett, Brydon L, Chung, K Fan
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Sprache:eng
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Zusammenfassung: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
ISSN:0007-1188
1476-5381
DOI:10.1038/sj.bjp.0705569