title: The effect of serine protease inhibitors on airway inflammation in a chronic allergen-induced asthma mouse model.
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.
authors.affiliation: Graduate Institute of Chinese Medicine, China Medical University, Taichung 40402, Taiwan.
authors.forename: Chih-Che
authors.identifier: 0000-0003-3122-6806
authors.initials: CC
authors.lastname: Lin
authors.affiliation: School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan.
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Lin
authors.affiliation: School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan.
authors.forename: Shulhn-Der
authors.initials: SD
authors.lastname: Wang
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 40402, Taiwan.
authors.forename: Chung-Jen
authors.initials: CJ
authors.lastname: Chiang
authors.affiliation: Department of Chemical Engineering, Feng Chia University, Taichung 40724, Taiwan.
authors.forename: Yun-Peng
authors.identifier: 0000-0001-7997-0752
authors.initials: YP
authors.lastname: Chao
authors.affiliation: School of Medicine, Semmelweis University, Budapest 1085, Hungary.
authors.forename: Joseph
authors.identifier: 0000-0003-0623-816X
authors.initials: J
authors.lastname: Lin
authors.affiliation: School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan ; Department of Chinese Medicine, China Medical University Hospital, Taichung 40402, Taiwan.
authors.forename: Shung-Te
authors.initials: ST
authors.lastname: Kao
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma; D001550:Benzamidines; D004195:Disease Models, Animal; D016670:Gabexate / Q000627:therapeutic use; D006023:Glycoproteins / Q000627:therapeutic use; D006146:Guanidines / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology*; D018793:Interleukin-13 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*
chemical_list: D000485:Allergens; D001550:Benzamidines; D006023:Glycoproteins; D006146:Guanidines; D018793:Interleukin-13; D020381:Interleukin-17; D015848:Interleukin-5; D015850:Interleukin-6; D016328:NF-kappa B; D015842:Serine Proteinase Inhibitors; D015847:Interleukin-4; D016670:Gabexate; C028665:urinastatin; C032855:nafamostat