Induction and regulation of matrix metalloproteinase-12in human airway smooth muscle cells
<p>Abstract</p> <p>Background</p> <p>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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2005-12-01
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| Series: | Respiratory Research |
| Online Access: | http://respiratory-research.com/content/6/1/148 |
| _version_ | 1818834366349967360 |
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| author | Papi Alberto Bhavsar Pankaj K Oltmanns Ute Sukkar Maria B Issa Razao Xie Shaoping Caramori Gaetano Adcock Ian Fan Chung K |
| author_facet | Papi Alberto Bhavsar Pankaj K Oltmanns Ute Sukkar Maria B Issa Razao Xie Shaoping Caramori Gaetano Adcock Ian Fan Chung K |
| author_sort | Papi Alberto |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>We provide evidence that MMP-12 mRNA and protein are expressed by <it>in-situ </it>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)-1β, 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-1β on MMP-12, indicating a role for these kinases in IL-1β-induced induction and release of MMP-12. IL-1β-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)-α through enhancing activator protein-1 activation by IL-1β. Transforming growth factor-β had no significant effect on MMP-12 induction.</p> <p>Conclusion</p> <p>Our findings indicate that human airway smooth muscle cells express and secrete MMP-12 that is up-regulated by IL-1β and TNF-α. 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.</p> |
| first_indexed | 2024-12-19T02:33:40Z |
| format | Article |
| id | doaj.art-d5505a9b0af44d7ea9358bdf672b4d22 |
| institution | Directory Open Access Journal |
| issn | 1465-9921 |
| language | English |
| last_indexed | 2024-12-19T02:33:40Z |
| publishDate | 2005-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-d5505a9b0af44d7ea9358bdf672b4d222022-12-21T20:39:33ZengBMCRespiratory Research1465-99212005-12-016114810.1186/1465-9921-6-148Induction and regulation of matrix metalloproteinase-12in human airway smooth muscle cellsPapi AlbertoBhavsar Pankaj KOltmanns UteSukkar Maria BIssa RazaoXie ShaopingCaramori GaetanoAdcock IanFan Chung K<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>We provide evidence that MMP-12 mRNA and protein are expressed by <it>in-situ </it>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)-1β, 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-1β on MMP-12, indicating a role for these kinases in IL-1β-induced induction and release of MMP-12. IL-1β-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)-α through enhancing activator protein-1 activation by IL-1β. Transforming growth factor-β had no significant effect on MMP-12 induction.</p> <p>Conclusion</p> <p>Our findings indicate that human airway smooth muscle cells express and secrete MMP-12 that is up-regulated by IL-1β and TNF-α. 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.</p>http://respiratory-research.com/content/6/1/148 |
| spellingShingle | Papi Alberto Bhavsar Pankaj K Oltmanns Ute Sukkar Maria B Issa Razao Xie Shaoping Caramori Gaetano Adcock Ian Fan Chung K Induction and regulation of matrix metalloproteinase-12in human airway smooth muscle cells Respiratory Research |
| title | Induction and regulation of matrix metalloproteinase-12in human airway smooth muscle cells |
| title_full | Induction and regulation of matrix metalloproteinase-12in human airway smooth muscle cells |
| title_fullStr | Induction and regulation of matrix metalloproteinase-12in human airway smooth muscle cells |
| title_full_unstemmed | Induction and regulation of matrix metalloproteinase-12in human airway smooth muscle cells |
| title_short | Induction and regulation of matrix metalloproteinase-12in human airway smooth muscle cells |
| title_sort | induction and regulation of matrix metalloproteinase 12in human airway smooth muscle cells |
| url | http://respiratory-research.com/content/6/1/148 |
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