Role of c-jun N-terminal kinase in the induced release of GM-CSF, RANTES and IL-8 from human airway smooth muscle cells

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作者：

U Oltmanns，R Issa，MB Sukkar，M John，KF Chung

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摘要：

Human airway smooth muscle cells (HASMC) contribute to airway inflammation in asthma by virtue of their capacity to produce several inflammatory mediators including IL-8, GM-CSF and RANTES. The intracellular signal pathway underlying the production of these cytokines in HASMC is not entirely elucidated. We examined the role of the mitogen-activated protein kinase (MAPK) c-jun N-terminal kinase (JNK) in TNF ± - and IL-1 -induced GM-CSF, RANTES and IL-8 production in HASMC by using a novel specific inhibitor for JNK (SP600125). Confluent HASMC were treated with TNF ± or IL-1 (10 ng ml 1 ) for 24 h in the presence or absence of SP600125 (1100 M ). JNK activity was determined by a kinase assay. Phosphorylation of JNK, p38 MAPK and ERK was examined by Western blotting. Culture supernatants were assayed for GM-CSF, RANTES and IL-8 content by ELISA. Maximum TNF ± - or IL-1 -induced phosphorylation of JNK in HASMC occurred after 15 min and returned to baseline levels after 4 h. SP600125 inhibited TNF ± - and IL-1 -induced JNK activity in HASMC as shown by the reduced phosphorylation of its substrate c-jun. Furthermore, GM-CSF, RANTES and to a lesser extent IL-8 release from HASMC treated with TNF ± and IL-1 was inhibited dosedependently by SP600125. JNK activation is involved in TNF ± - and IL-1 -induced GM-CSF, RANTES and IL-8 production from HASMC. JNK may therefore represent a critical pathway for cytokine production in HASMC. British Journal of Pharmacology (2003) 139 , 12281234. doi: [DOI link]

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关键词：

c-jun N-terminal kinase airway smooth muscle cells cytokines asthma airway inflammation signal transduction

DOI：

10.1038/sj.bjp.0705345

被引量：

239

年份：

2010