Effects of the serine protease inhibitor rBmTI-A in an experimental mouse model of chronic allergic pulmonary inflammation

Sci Rep. 2019 Sep 2;9(1):12624. doi: 10.1038/s41598-019-48577-4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Bronchoalveolar Lavage Fluid
  • Chronic Disease
  • Disease Models, Animal
  • Eosinophils / drug effects
  • Extracellular Matrix / metabolism
  • Hypersensitivity / complications*
  • Hypersensitivity / drug therapy*
  • Hypersensitivity / physiopathology
  • Lung / pathology
  • Lung / physiopathology
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mice, Inbred BALB C
  • Pneumonia / complications*
  • Pneumonia / drug therapy*
  • Pneumonia / physiopathology
  • Proteolysis
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use*
  • Respiratory Mechanics / drug effects
  • Serine Proteinase Inhibitors / therapeutic use*

Substances

  • Biomarkers
  • Recombinant Proteins
  • Serine Proteinase Inhibitors
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 1