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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2007-5-21
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pubmed:abstractText |
Expression of the inflammatory chemokine, growth-related oncogene protein-alpha (GRO-alpha), from airway smooth muscle cells (ASMC) is regulated by pathways involving NF-kappaB and MAPK activation. We determined the effects of dexamethasone on GRO-alpha induced by IL-1beta or TNF-alpha with respect to the role of MAPK pathways and of MAPK phosphatase-1 (MKP-1). Human ASMC were studied in primary culture at confluence. Dexamethasone (10(-8)-10(-5) M) partially inhibited GRO-alpha expression and release induced by IL-1beta and TNF-alpha; this was associated with an inhibition of JNK, but not of p38 or ERK phosphorylation. Together with IL-1beta or TNF-alpha, dexamethasone rapidly induced mRNA and protein expression of MKP-1, which dephosphorylates MAPKs. Using MKP-1 small interfering RNA (siRNA) to block the expression of IL-1beta- and dexamethasone-induced MKP-1 by 50%, JNK phosphorylation was doubled. The inhibitory effect of dexamethasone on GRO-alpha release was partially reversed in ASMC treated with MKP-1 siRNA compared with those treated with scrambled siRNA. In contrast, overexpression of MKP-1 led to a reduction in IL-1beta-induced release of GRO-alpha, but the inhibitory effects of dexamethasone were preserved. Nuclear translocation of the glucocorticoid receptor was increased in ASMC exposed to dexamethasone and IL-1beta. Using chromatin immunoprecipitation assay, glucocorticoid receptor binding to the MKP-1 promoter was increased by IL-1beta and dexamethasone compared with either alone. Glucocorticoids and IL-1beta or TNF-alpha modulate GRO-alpha release partly through the inhibition of JNK pathway, resulting from an up-regulation of MKP-1 expression.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CXCL1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL1,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, CXC,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DUSP1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/Dual Specificity Phosphatase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Immediate-Early Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1beta,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoprotein Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Phosphatase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glucocorticoid
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
178
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7366-75
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:17513787-Active Transport, Cell Nucleus,
pubmed-meshheading:17513787-Bronchi,
pubmed-meshheading:17513787-Cell Cycle Proteins,
pubmed-meshheading:17513787-Cells, Cultured,
pubmed-meshheading:17513787-Chemokine CXCL1,
pubmed-meshheading:17513787-Chemokines, CXC,
pubmed-meshheading:17513787-DNA,
pubmed-meshheading:17513787-Dexamethasone,
pubmed-meshheading:17513787-Dual Specificity Phosphatase 1,
pubmed-meshheading:17513787-Humans,
pubmed-meshheading:17513787-Immediate-Early Proteins,
pubmed-meshheading:17513787-Interleukin-1beta,
pubmed-meshheading:17513787-Muscle, Smooth,
pubmed-meshheading:17513787-NF-kappa B,
pubmed-meshheading:17513787-Phosphoprotein Phosphatases,
pubmed-meshheading:17513787-Protein Binding,
pubmed-meshheading:17513787-Protein Phosphatase 1,
pubmed-meshheading:17513787-Protein Tyrosine Phosphatases,
pubmed-meshheading:17513787-RNA, Messenger,
pubmed-meshheading:17513787-RNA, Small Interfering,
pubmed-meshheading:17513787-Receptors, Glucocorticoid,
pubmed-meshheading:17513787-Transfection,
pubmed-meshheading:17513787-Up-Regulation
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pubmed:year |
2007
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pubmed:articleTitle |
Corticosteroid inhibition of growth-related oncogene protein-alpha via mitogen-activated kinase phosphatase-1 in airway smooth muscle cells.
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pubmed:affiliation |
Experimental Medicine, Airway Studies Section, National Heart and Lung Institute, Imperial College, London, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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