Abstract |
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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Authors | Chih-Che Lin, Li-Jen Lin, Shulhn-Der Wang, Chung-Jen Chiang, Yun-Peng Chao, Joseph Lin, Shung-Te Kao |
Journal | Mediators of inflammation
(Mediators Inflamm)
Vol. 2014
Pg. 879326
( 2014)
ISSN: 1466-1861 [Electronic] United States |
PMID | 25180025
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Allergens
- Benzamidines
- Glycoproteins
- Guanidines
- Interleukin-13
- Interleukin-17
- Interleukin-5
- Interleukin-6
- NF-kappa B
- Serine Proteinase Inhibitors
- Interleukin-4
- Gabexate
- urinastatin
- nafamostat
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Topics |
- Allergens
(immunology)
- Animals
- Asthma
- Benzamidines
- Disease Models, Animal
- Gabexate
(therapeutic use)
- Glycoproteins
(therapeutic use)
- Guanidines
(therapeutic use)
- Inflammation
(drug therapy, immunology)
- Interleukin-13
(metabolism)
- Interleukin-17
(metabolism)
- Interleukin-4
(metabolism)
- Interleukin-5
(metabolism)
- Interleukin-6
(metabolism)
- Male
- Mice
- Mice, Inbred BALB C
- NF-kappa B
(metabolism)
- Serine Proteinase Inhibitors
(therapeutic use)
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