Abstract
Aims: To evaluate if a plant Kunitz proteinase inhibitor BbKI contributes to inactivation of elastase-induced inflammatory and extracellular matrix remodelling alterations. Methods: C57Bl6 mice received elastase (50ml/animal/intratracheal-E-group) or saline (Ve-group). Mice were treated with BbKI (2mg/kg) on days 1, 14, 21 after elastase instillation (I-E group) or saline instillation (I-Ve group). On day 30 mice were anesthetized, mechanically ventilated, lungs were removed and we quantified neutrophils, positive cells for MMP-9, MMP-12, TNF-a, MAC-2, TIMP, IL8, MUC5, iNOS, eNOS and volume fraction of elastic and collagen fibers and PGF2alpha in alveolar septa and airways. Results: In E-group, there was an increase of neutrophils, MMP-9, MMP-12, TNF-a, MAC-2, TIMP, IL8, MUC5, iNOS, eNOS, elastic and collagen fibers and isoprostanes in alveolar and/or airways compared to controls (p<0.05). In I-E group, there was a reduction in alveolar septa of neutrophils, positive cells for MMP-9, MMP-12, TNF-a, MAC-2, TIMP1, IL8, iNOS, eNOS, PGF2alpha, collagen and elastic fibers compared to E-group. Considering airways of I-E group, there was a decrease of neutrophils, positive cells for MMP-9, MMP-12, TNF-a, TIMP1, IL8, MUC5, iNOS, eNOS, PGF2alpha, elastic and collagen fibers compared to E-group (p<0.05). Conclusions: This proteinase inhibitor (BbKI) reduced elastase-induced pulmonary inflammatory and extracellular matrix remodeling alterations induced by elastase and this inhibitor may contribute as potential therapeutic tool for COPD management. Financial Support: FAPESP, CNPq, LIM-20 HC-FMUSP.
- © 2014 ERS