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http://purl.uniprot.org/citations/16359550http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16359550http://www.w3.org/2000/01/rdf-schema#comment"

Background

The elastolytic enzyme matrix metalloproteinase (MMP)-12 has been implicated in the development of airway inflammation and remodeling. We investigated whether human airway smooth muscle cells could express and secrete MMP-12, thereby participating in the pathogenesis of airway inflammatory diseases.

Methods

Laser capture microdissection was used to collect smooth muscle cells from human bronchial biopsy sections. MMP-12 mRNA expression was analysed by quantitative real-time RT-PCR. MMP-12 protein expression and secretion from cultured primary airway smooth muscle cells was further analysed by Western blot. MMP-12 protein localization in bronchial tissue sections was detected by immunohistochemistry. MMP-12 activity was determined by zymography. The TransAM AP-1 family kit was used to measure c-Jun activation and nuclear binding. Analysis of variance was used to determine statistical significance.

Results

We provide evidence that MMP-12 mRNA and protein are expressed by in-situ human airway smooth muscle cells obtained from bronchial biopsies of normal volunteers, and of patients with asthma, COPD and chronic cough. The pro-inflammatory cytokine, interleukin (IL)-1beta, induced a >100-fold increase in MMP-12 gene expression and a >10-fold enhancement in MMP-12 activity of primary airway smooth muscle cell cultures. Selective inhibitors of extracellular signal-regulated kinase, c-Jun N-terminal kinase and phosphatidylinositol 3-kinase reduced the activity of IL-1beta on MMP-12, indicating a role for these kinases in IL-1beta-induced induction and release of MMP-12. IL-1beta-induced MMP-12 activity and gene expression was down-regulated by the corticosteroid dexamethasone but up-regulated by the inflammatory cytokine tumour necrosis factor (TNF)-alpha through enhancing activator protein-1 activation by IL-1beta. Transforming growth factor-beta had no significant effect on MMP-12 induction.

Conclusion

Our findings indicate that human airway smooth muscle cells express and secrete MMP-12 that is up-regulated by IL-1beta and TNF-alpha. Bronchial smooth muscle cells may be an important source of elastolytic activity, thereby participating in remodeling in airway diseases such as COPD and chronic asthma."xsd:string
http://purl.uniprot.org/citations/16359550http://purl.org/dc/terms/identifier"doi:10.1186/1465-9921-6-148"xsd:string
http://purl.uniprot.org/citations/16359550http://purl.uniprot.org/core/author"Xie S."xsd:string
http://purl.uniprot.org/citations/16359550http://purl.uniprot.org/core/author"Chung K.F."xsd:string
http://purl.uniprot.org/citations/16359550http://purl.uniprot.org/core/author"Sukkar M.B."xsd:string
http://purl.uniprot.org/citations/16359550http://purl.uniprot.org/core/author"Bhavsar P.K."xsd:string
http://purl.uniprot.org/citations/16359550http://purl.uniprot.org/core/author"Issa R."xsd:string
http://purl.uniprot.org/citations/16359550http://purl.uniprot.org/core/author"Papi A."xsd:string
http://purl.uniprot.org/citations/16359550http://purl.uniprot.org/core/author"Caramori G."xsd:string
http://purl.uniprot.org/citations/16359550http://purl.uniprot.org/core/author"Oltmanns U."xsd:string
http://purl.uniprot.org/citations/16359550http://purl.uniprot.org/core/author"Adcock I."xsd:string
http://purl.uniprot.org/citations/16359550http://purl.uniprot.org/core/date"2005"xsd:gYear
http://purl.uniprot.org/citations/16359550http://purl.uniprot.org/core/name"Respir Res"xsd:string
http://purl.uniprot.org/citations/16359550http://purl.uniprot.org/core/pages"148"xsd:string
http://purl.uniprot.org/citations/16359550http://purl.uniprot.org/core/title"Induction and regulation of matrix metalloproteinase-12 in human airway smooth muscle cells."xsd:string
http://purl.uniprot.org/citations/16359550http://purl.uniprot.org/core/volume"6"xsd:string
http://purl.uniprot.org/citations/16359550http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/16359550
http://purl.uniprot.org/citations/16359550http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/16359550
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