Disclosing the involvement of proteases in an eczema murine animal model: Perspectives for protease inhibitor-based therapies

• DOI: 10.1016/j.biochi.2021.12.003
• Publication Date: 2021-12-09T16:32:07Z
• Authors: Ilana Cruz-Silva; Viviane Abreu Nunes; Mariana Rydlewski; Andrezza Justino ...; Priscila Praxedes...; Adriana Aparecida...; Aparecida Sadae T...; Mariana da Silva ...
• Keywords: Mice; 03 medical and health sciences; Cathepsin G; 0302 clinical medicine; Neutrophils; Eczema; Animals; Protease Inhibitors; Cathepsins; Peptide Hydrolases; 3. Good health

Eczema is a skin condition characterized by itchy and inflammatory patches. The accumulation of neutrophils and the imbalance between enzymes and their inhibitors appears to be related to this condition. We proposed a neutrophil elastase (NE)-based eczema model in mice in order to verify histopathological features as well as the expression and activity of proteases and inhibitors. Mice skins were topically administered with human NE (0-2 pmol/cm2) for 24-168 h. It was observed thickening of epidermis, parakeratosis, spongiosis and leukocyte infiltration. Also, NE-treated skins presented high activity of epidermal kallikreins 5 and 7, and cathepsin B on synthetic substrates, and expression evaluated by RT-qPCR. The proteolytic activity was inhibited by soybean trypsin inhibitor, CA074 and Caesalpinia echinata kallikrein inhibitor (CeKI). The topic application of CeKI reversed eczema phenotype in NE-treated skins. Elafin expression was shown to be increased in NE-treated skins. These results suggest that the NE may trigger morphological and biochemical changes in skin similar to those observed in eczematous diseases. In addition to the establishment of this in vivo model, this work opens perspectives for the use of protease inhibitor-based drugs for the management of this skin condition.