| Autor: |
Raju Allam, Venkata Sita Rama, Waern, Ida, Taha, Sowsan, Akula, Srinivas, Wernersson, Sara, Pejler, Gunnar |
| Předmět: |
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| Zdroj: |
Frontiers in Immunology; 2023, p1-14, 14p |
| Abstrakt: |
Introduction: Asthma is characterized by an imbalance between proteases and their inhibitors. Hence, an attractive therapeutic option could be to interfere with asthma-associated proteases. Here we exploited this option by assessing the impact of nafamostat, a serine protease inhibitor known to neutralize mast cell tryptase. Methods: Nafamostat was administered in a mouse model for asthma based on sensitization by house dust mite (HDM) extract, followed by the assessment of effects on airway hyperreactivity, inflammatory parameters and gene expression. Results: We show that nafamostat efficiently suppressed the airway hyperreactivity in HDM-sensitized mice. This was accompanied by reduced infiltration of eosinophils and lymphocytes to the airways, and by lower levels of pro-inflammatory compounds within the airway lumen. Further, nafamostat had a dampening impact on goblet cell hyperplasia and smooth muscle layer thickening in the lungs of HDM-sensitized animals. To obtain deeper insight into the underlying mechanisms, a transcriptomic analysis was conducted. This revealed, as expected, that the HDM sensitization caused an upregulated expression of numerous pro-inflammatory genes. Further, the transcriptomic analysis showed that nafamostat suppressed the levels of multiple proinflammatory genes, with a particular impact on genes related to asthma. Discussion: Taken together, this study provides extensive insight into the ameliorating effect of nafamostat on experimental asthma, and our findings can thereby provide a basis for the further evaluation of nafamostat as a potential therapeutic agent in human asthma. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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