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.

Ixodes ricinus Salivary Serpin IRS-2 Affects Th17 Differentiation via Inhibition of the Interleukin-6/STAT-3 Signaling Pathway

“…A causative protein, neutrophil-activating protein A (NapA) from B. burgdorferi, which is able to stimulate IL-17 production in synovial-fluid-derived T cells and could thus be crucial for the induction and maintenance of Lyme arthritis, was identified (45). Moreover, it is well described that synthetic or human-derived serpins, which are commonly used in the treatment of many autoimmune diseases, are able to decrease Th17 differentiation (6).…”

“…These effects were associated with inhibition of Th2 cytokines (interleukin-4 [IL-4], IL-5, IL-6, and IL-13) and Th17 cell functions. These serpins also inhibited NF-B activation in lung tissues (6).…”

Antioxidant capacity of banana peel and its modulation of Nrf2-ARE associated gene expression in broiler chickens

“…), according to the manufacture's protocols. Total mRNA was reverse-transcribed into cDNA and the expression levels were analysed by qPCR, following the methods of Lin et al (2014). All determined genes were normalised using b-actin as the internal control and calculated via the 2 ÀDDCt method.…”

An Imbalance between Proteases and Endogenous Protease Inhibitors in Eosinophilic Airway Disease

“…Netherton syndrome, due to inheritance of loss-offunction mutations in both copies of SPINK5, causes dermatological pathology and also elevated IgE levels often with an eosinophilia, however such mutations are rare (7). Importantly, there are associations between polymorphisms in EPIs such as SPINK5 and asthma, and these polymorphisms may provide a small contribution to the aetiology of these eosinophilic airways diseases (8) Ultimately, one may envisage a future in which manipulation of EPIs and/or protease inhibition may provide a novel therapeutic option in eosinophilic airways diseases (13), perhaps with measurement of sputum protease activity used as a biomarker to titrate therapy.…”