A Plasminogen Activator Inhibitor-1 Inhibitor Reduces Airway Remodeling in a Murine Model of Chronic Asthma
| Autor: | Robert P. Schleimer, Seong H. Cho, Mesut Eren, Sun H. Lee, Douglas E. Vaughan |
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| Rok vydání: | 2012 |
| Předmět: |
Pulmonary and Respiratory Medicine
Clinical Biochemistry Mice chemistry.chemical_compound Oral administration Plasminogen Activator Inhibitor 1 medicine Animals Molecular Biology Asthma Lung medicine.diagnostic_test biology business.industry Articles Cell Biology respiratory system medicine.disease respiratory tract diseases Mice Inbred C57BL Disease Models Animal Ovalbumin Bronchoalveolar lavage medicine.anatomical_structure chemistry Plasminogen activator inhibitor-1 Chronic Disease Immunology biology.protein Airway business Plasminogen activator |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 46:842-846 |
| ISSN: | 1535-4989 1044-1549 |
| Popis: | We previously reported that plasminogen activator inhibitor (PAI)-1 deficiency prevents collagen deposition in the airways of ovalbumin (OVA)-challenged mice. In this study, we explored the therapeutic utility of blocking PAI-1 in preventing airway remodeling, using a specific PAI-1 inhibitor, tiplaxtinin. C57BL/6J mice were immunized with intraperitoneal injections of OVA on Days 0, 3, and 6. Starting on Day 11, mice were challenged with phosphate-buffered saline or OVA by nebulization three times per week for 4 weeks. Tiplaxtinin was mixed with chow and administered orally from 1 day before the phosphate-buffered saline or OVA challenge. Lung tissues were harvested after challenge and characterized histologically for infiltrating inflammatory cells, mucus-secreting goblet cells, and collagen deposition. Airway hyperresponsiveness was measured using whole-body plethysmography. Tiplaxtinin treatment significantly decreased levels of PAI-1 activity in bronchoalveolar lavage fluids, which indicates successful blockage of PAI-1 activity in the airways. The number of infiltrated inflammatory cells was reduced by tiplaxtinin treatment in the lungs of the OVA-challenged mice. Furthermore, oral administration of tiplaxtinin significantly attenuated the degree of goblet cell hyperplasia and collagen deposition in the airways of the OVA-challenged mice, and methacholine-induced airway hyperresponsiveness was effectively reduced by tiplaxtinin in these animals. This study supports our previous findings that PAI-1 promotes airway remodeling in a murine model of chronic asthma, and suggests that PAI-1 may be a novel target of treatment of airway remodeling in asthma. |
| Databáze: | OpenAIRE |
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