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| Title | Effects of Asthma Combination Therapy on Extracellular Matrix Remodeling in Human Lung Fibroblasts |
| Author/s | Lizbet Todorova |
| Department/s |
Lung Biology
|
| Full-text | Available as PDF |
| Defence date | 2007-12-21 |
| Defence time | 13:00 |
| Defence place | GK-salen |
| Opponent | Professor Sven-Erik Dahlén |
| Publication/Series | Lund University, Faculty of Medicine Doctoral Dissertation Series |
| Publishing year | 2007 |
| Volume | 2007:172 |
| Pages | 137 |
| Document type | Dissertation |
| Language | English |
| Publisher | Lung Biology |
| Abstract English |
Fibroblasts, being one of the resident and structural cells of the lung, have the capacity to produce inflammatory mediators, cytokines and extracellular matrix (ECM) proteins perpetuating the inflammation in the airways of asthmatics. Airway remodeling is also a prominent feature of asthma that affects the lung function causing a thickening of the airways. An increased ECM production of proteoglycans, collagens and other ECM molecules, usually accompanied by dysfunction of the ECM degrading enzymes, the metalloproteinases, may not only contribute to a subepithelial fibrosis formation, but it may also be a compartment where accumulating ECM sequesters and stores inflammatory mediators. Lung fibroblasts are the major producers of ECM components within the lung and may initiate, regulate and contribute to the airway remodeling in asthma. Current asthma treatments based on anti-inflammatory glucocorticoids (GC) and bronchodilatory long acting β2-agonists (LABA) are known to improve lung function, especially when administered in combination. Airway remodeling is relatively resistant to treatment with GC, but may respond better if treated with a combination of GC and LABA. The results from this thesis, suggest that indeed, combination of GC and LABA, via complementary and additive actions, has greater potential than GC monotherapy to counteract progression of airway remodeling. By reducing the levels of the major ECM components such as proteoglycans and collagen I, treatment with combination therapy may resolve an accumulating ECM and re-establish normal ECM deposition in asthmatics. |
| Subject |
Medicine and Health Sciences |
| Keywords | Proteoglycans, Asthma, Lung fibroblasts, Collagen, Airway remodeling, TGFβ, Glucocorticoids, Combination therapy., β2-agonist, MMPs |
| ISBN/ISSN/Other |
ISSN: 1652-8220 ISBN: 978-91-85897-50-6 |
| Supervisor | Gunilla Westergren-Thorsson |
| Supervisor | Anders Malmström |
| Supervisor | Anna Miller-Larsson |
| Part of | Lung Fibroblast Proteoglycan Production Induced by Serum is Inhibited by Budesonide and Formoterol. |
