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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Main Authors: Chih-Che Lin, Li-Jen Lin, Shulhn-Der Wang, Chung-Jen Chiang, Yun-Peng Chao, Joseph Lin, Shung-Te Kao
Format: Article
Language:English
Published: Wiley 2014-01-01
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.
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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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