ABSTRACT
BACKGROUND: Allergen source-derived proteases are a critical factor in the formation and development of asthma. The cysteine protease activity of house dust mite (HDM) disrupts the epithelial barrier function. The expression of cystatin SN (CST1) is elevated in asthma epithelium. CST1 inhibits the cysteine protease activity. We aimed to elucidate the role of epithelium-derived CST1 in the development of asthma caused by HDM. METHODS: CST1 protein levels in sputum supernatants and serum of patients with asthma and healthy volunteers were measured by ELISA. The ability of CST1 protein to suppress HDM-induced bronchial epithelial barrier function was examined in vitro. The effects of exogenous CST1 protein on abrogating HDM-induced epithelial barrier function and inflammation were examined in mice in vivo. RESULTS: CST1 protein levels were higher in sputum supernatants (142.4 ± 8.95 vs 38.87 ± 6.85 ng/mL, P < 0.0001) and serum (1129 ± 73.82 vs 703.1 ± 57.02 pg/mL, P = 0.0035) in patients with asthma than in healthy subjects. The levels were significantly higher in patients with not well- and very poorly controlled asthma than those with well-controlled asthma. Sputum and serum CST1 protein levels were negatively correlated with lung function in asthma. CST1 protein levels were significantly lower in the serum of HDM-specific IgE (sIgE)-positive asthmatics than in sIgE-negative asthmatics. The HDM-induced epithelial barrier function disruption was suppressed by recombinant human CST1 protein (rhCST1) in vitro and in vivo. CONCLUSION: Our data indicated that human CST1 protein suppresses asthma symptoms by protecting the asthmatic bronchial epithelial barrier through inhibiting allergenic protease activity. CST1 protein may serve as a potential biomarker for asthma control.
Subject(s)
Asthma , Cysteine Proteases , Humans , Mice , Animals , Pyroglyphidae , Salivary Cystatins , Asthma/etiology , Dermatophagoides pteronyssinus , Allergens , Epithelium , Peptide Hydrolases , Antigens, Dermatophagoides , DustABSTRACT
Solutions of poly(ether ether ketone) in dichloroacetic acid have been shown to form monolithic, thermoreversible gels at temperatures ranging from 10 to 140 °C. A phase diagram was constructed over broad concentration and temperature ranges, and the phase boundary suggests an upper critical solution temperature (UCST) behavior. Furthermore, poly(ether ether ketone) (PEEK) gels were solvent-exchanged with water to form hydrogels and subsequently lyophilized to form PEEK aerogels. The PEEK aerogels of density 0.2 g/mL were found to be highly porous and composed of uniform 200 nm morphological features. The crystal structure of the PEEK hydrogels and aerogels was found to be identical to that of melt-crystallized PEEK. The mechanical properties of the PEEK aerogels (in compression) were found to be superior to conventional silicate aerogels of comparable density. This report is the first example of a monolithic, thermoreversible gel of PEEK and the first demonstration of PEEK hydrogels and aerogels.
