Abstract
To evaluate whether a recombinant serine protease inhibitor (rBmTI-A) modulates inflammation in an experimental model of chronic allergic lung inflammation. Balb/c mice were divided into four groups: SAL (saline), OVA (sensitized with ovalbumin), SAL + rBmTI-A (control treated with rBmTI-A) and OVA + rBmTI-A (sensitized with ovalbumin and treated with rBmTI-A). The animals received an intraperitoneal injection of saline or ovalbumin, according to the group. The groups received inhalation with saline or ovalbumin and were treated with rBmTI-A or saline by nasal instillation. After 29 days, we evaluated the respiratory mechanics; bronchoalveolar lavage fluid (BALF); cytokines; MMP-9, TIMP-1; eosinophils; collagen and elastic fibre expression in the airways; and the trypsin-like, MMP-1, and MMP-9 lung tissue proteolytic activity. Treatment with rBmTI-A reduced the trypsin-like proteolytic activity, the elastance and resistance maximum response, the polymorphonuclear cells, IL-5, IL-10, IL-13 and IL-17A in the BALF, the expression of IL-5, IL-13, IL-17, CD4+, MMP-9, TIMP-1, eosinophils, collagen and elastic fibres in the airways of the OVA + rBmTI-A group compared to the OVA group (p < 0.05). rBmTI-A attenuated bronchial hyperresponsiveness, inflammation and remodelling in this experimental model of chronic allergic pulmonary inflammation. This inhibitor may serve as a potential therapeutic tool for asthma treatment.
Highlights
To evaluate whether a recombinant serine protease inhibitor modulates inflammation in an experimental model of chronic allergic lung inflammation
We evaluated the effect of the serine protease inhibitor rBmTI-A in an experimental model of chronic allergic pulmonary inflammation
Compared to those of the controls, this result, in the animals that were sensitized with ovalbumin and that were treated with rBmTI-A, was associated with the attenuation of airway hyperresponsiveness after challenge with the bronchoconstrictor methacholine; the reduction of eosinophil numbers in the bronchoalveolar lavage fluid (BALF) and in the airways; decreased expression of Th2/Th17 (IL-5, IL-10, IL-13 and IL-17) inflammatory cytokines in the BALF and in the airways; the reduction of CD4+ positive cells in the airways; attenuation of the MMP-9 and TIMP-1 expression in the airways; and the decrease of the extracellular matrix remodelling, as evaluated by the reduction of the collagen and elastic fibre content in the airways
Summary
To evaluate whether a recombinant serine protease inhibitor (rBmTI-A) modulates inflammation in an experimental model of chronic allergic lung inflammation. RBmTI-A attenuated bronchial hyperresponsiveness, inflammation and remodelling in this experimental model of chronic allergic pulmonary inflammation. This inhibitor may serve as a potential therapeutic tool for asthma treatment. There is evidence that an imbalance between proteases and their inhibitors plays an important role in the development of asthma[4]. This effect can be observed more clearly in periods of exacerbation[5]. Some protease inhibitors have been tested, and their potential airway anti-inflammatory effects have been demonstrated[7,8,9]
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