The Effect of Serine Protease Inhibitors on Airway Inflammation in a Chronic Allergen-Induced Asthma Mouse Model
Serine protease inhibitors reportedly attenuated airway inflammation and had antioxidant in multiorgan. However, the effects of the serine protease inhibitors nafamostat mesilate (FUT), gabexate mesilate (FOY), and ulinastatin (UTI) on a long-term challenged mouse model of chronic asthma are unclear...
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Wiley
2014-01-01
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Series: | Mediators of Inflammation |
Online Access: | http://dx.doi.org/10.1155/2014/879326 |
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author | Chih-Che Lin Li-Jen Lin Shulhn-Der Wang Chung-Jen Chiang Yun-Peng Chao Joseph Lin Shung-Te Kao |
author_facet | Chih-Che Lin Li-Jen Lin Shulhn-Der Wang Chung-Jen Chiang Yun-Peng Chao Joseph Lin Shung-Te Kao |
author_sort | Chih-Che Lin |
collection | DOAJ |
description | Serine protease inhibitors reportedly attenuated airway inflammation and had antioxidant in multiorgan. However, the effects of the serine protease inhibitors nafamostat mesilate (FUT), gabexate mesilate (FOY), and ulinastatin (UTI) on a long-term challenged mouse model of chronic asthma are unclear. BALB/c mice (6 mice/group) were intratracheally inoculated with five doses of Dermatophagoides pteronyssinus (Der p; 50 μL, 1 mg/mL) at one-week intervals. Therapeutic doses of FUT (0.0625 mg/kg), FOY (20 mg/kg), or UTI (10,000 U/kg) were, respectively, injected intraperitoneally into these mice. Control mice received sterile PBS. At 3 days after the last challenge, mice were sacrificed to assess airway hyperresponsiveness (AHR), remodeling, and inflammation; lung histological features; and cytokine expression profiles. Compared with untreated controls, mice treated with FUT, FOY, and UTI had decreased AHR and goblet cell hyperplasia, decreased eosinophil and neutrophil infiltration, decreased Der p-induced IL-4 levels in serum and IL-5, IL-6, IL-13, and IL-17 levels in bronchoalveolar lavage fluid, and inhibited nuclear factor (NF)-κB activity in lung tissues. The serine protease inhibitors FUT, FOY, and UTI have potential therapeutic benefits for treating asthma by downregulating Th2 cytokines and Th17 cell function and inhibiting NF-κB activation in lung tissue. |
format | Article |
id | doaj-art-3f34573e9bb04fc492ff709a15c47bcc |
institution | Kabale University |
issn | 0962-9351 1466-1861 |
language | English |
publishDate | 2014-01-01 |
publisher | Wiley |
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series | Mediators of Inflammation |
spelling | doaj-art-3f34573e9bb04fc492ff709a15c47bcc2025-02-03T00:59:48ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/879326879326The Effect of Serine Protease Inhibitors on Airway Inflammation in a Chronic Allergen-Induced Asthma Mouse ModelChih-Che Lin0Li-Jen Lin1Shulhn-Der Wang2Chung-Jen Chiang3Yun-Peng Chao4Joseph Lin5Shung-Te Kao6Graduate Institute of Chinese Medicine, China Medical University, Taichung 40402, TaiwanSchool of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, TaiwanSchool of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, TaiwanDepartment of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 40402, TaiwanDepartment of Chemical Engineering, Feng Chia University, Taichung 40724, TaiwanSchool of Medicine, Semmelweis University, Budapest 1085, HungarySchool of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, TaiwanSerine protease inhibitors reportedly attenuated airway inflammation and had antioxidant in multiorgan. However, the effects of the serine protease inhibitors nafamostat mesilate (FUT), gabexate mesilate (FOY), and ulinastatin (UTI) on a long-term challenged mouse model of chronic asthma are unclear. BALB/c mice (6 mice/group) were intratracheally inoculated with five doses of Dermatophagoides pteronyssinus (Der p; 50 μL, 1 mg/mL) at one-week intervals. Therapeutic doses of FUT (0.0625 mg/kg), FOY (20 mg/kg), or UTI (10,000 U/kg) were, respectively, injected intraperitoneally into these mice. Control mice received sterile PBS. At 3 days after the last challenge, mice were sacrificed to assess airway hyperresponsiveness (AHR), remodeling, and inflammation; lung histological features; and cytokine expression profiles. Compared with untreated controls, mice treated with FUT, FOY, and UTI had decreased AHR and goblet cell hyperplasia, decreased eosinophil and neutrophil infiltration, decreased Der p-induced IL-4 levels in serum and IL-5, IL-6, IL-13, and IL-17 levels in bronchoalveolar lavage fluid, and inhibited nuclear factor (NF)-κB activity in lung tissues. The serine protease inhibitors FUT, FOY, and UTI have potential therapeutic benefits for treating asthma by downregulating Th2 cytokines and Th17 cell function and inhibiting NF-κB activation in lung tissue.http://dx.doi.org/10.1155/2014/879326 |
spellingShingle | Chih-Che Lin Li-Jen Lin Shulhn-Der Wang Chung-Jen Chiang Yun-Peng Chao Joseph Lin Shung-Te Kao The Effect of Serine Protease Inhibitors on Airway Inflammation in a Chronic Allergen-Induced Asthma Mouse Model Mediators of Inflammation |
title | The Effect of Serine Protease Inhibitors on Airway Inflammation in a Chronic Allergen-Induced Asthma Mouse Model |
title_full | The Effect of Serine Protease Inhibitors on Airway Inflammation in a Chronic Allergen-Induced Asthma Mouse Model |
title_fullStr | The Effect of Serine Protease Inhibitors on Airway Inflammation in a Chronic Allergen-Induced Asthma Mouse Model |
title_full_unstemmed | The Effect of Serine Protease Inhibitors on Airway Inflammation in a Chronic Allergen-Induced Asthma Mouse Model |
title_short | The Effect of Serine Protease Inhibitors on Airway Inflammation in a Chronic Allergen-Induced Asthma Mouse Model |
title_sort | effect of serine protease inhibitors on airway inflammation in a chronic allergen induced asthma mouse model |
url | http://dx.doi.org/10.1155/2014/879326 |
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