The Plant Proteinase InhibitorCrataBLPlays a Role in Controlling Asthma Response in Mice

Abstract

Background. CrataBL is a protein isolated from Crataeva tapia bark. It has been shown to exhibit several biological properties, including anti-inflammatory, analgesic, antitumor, and insecticidal activities. There are no studies evaluating the role of CrataBL in experimental asthma models. Aim. To evaluate the effects of CrataBL on lung mechanics, inflammation, remodeling, and oxidative stress activation of mice with allergic pulmonary inflammation. Materials and Methods. BALB/c mice (6-7 weeks old, 25-30g) were divided into four groups: nonsensitized and nontreated mice (C group, n=8); ovalbumin- (OVA-) sensitized and nontreated mice (OVA group, n=8); nonsensitized and CrataBL-treated mice (C+CR group, n=8); OVA-sensitized and CrataBL-treated mice (OVA+CR group, n=8). We evaluated hyperresponsiveness to methacholine, bronchoalveolar lavage fluid (BALF), pulmonary inflammation, extracellular matrix remodeling, and oxidative stress markers. Results. CrataBL treatment in OVA-sensitized mice (OVA+CR group) attenuated the following variables compared to OVA-sensitized mice without treatment (OVA group) (all p<0.05): (1) respiratory system resistance (Rrs) and elastance (Ers) after methacholine challenge; (2) total cells, macrophages, polymorphonuclear cells, and lymphocytes in BALF; (3) eosinophils and volume fraction of collagen and elastic fibers in the airway and alveolar wall according to histopathological and morphometry analysis; (4) IL-4-, IL-5-, IL-13-, IL-17-, IFN-γ-, MMP-9-, TIMP-1-, TGF-β-, iNOS-, and NF-kB-positive cells and volume of 8-iso-PGF2α in airway and alveolar septa according to immunohistochemistry; and (5) IL-4, IL-5, and IFN-γ according to an ELISA. Conclusion. CrataBL contributes to the control of hyperresponsiveness, pulmonary inflammation, extracellular matrix remodeling, and oxidative stress responses in an animal model of chronic allergic pulmonary inflammation.

Extracellular Matrix Component Remodeling in Respiratory Diseases: What Has Been Found in Clinical and Experimental Studies?

“…These components are likely secreted due to the activation of fibroblasts and myofibroblasts, mainly because of the TGF-β signaling [57,58]. Collagen fibers are the most abundant elements of the ECM in the lung, constituting approximately 70% of the lung tissue, and changing the structure, quantity, or geometry of their distribution can trigger changes in lung functioning [58,59,60].…”

“…Several studies using these experimental models of asthma have shown functional alterations in the resistance and elasticity of the respiratory system associated with inflammatory eosinophilic infiltrates; expression of Th2 and Th17 cytokines, MMP-9-, MMP-12-, TIMP-1-, and TGF-β-positive cells; increased deposition of actin, collagen, and elastic fibers, and increased mucus production in the airways and lung tissues [57,59,60,69,85].…”

Asthmatic Eosinophils Promote Contractility and Migration of Airway Smooth Muscle Cells and Pulmonary Fibroblasts In Vitro

“…However, we aimed to evaluate the asthmatic and healthy eosinophil effect on ASMC and PF contractility and differentiation into the contractile phenotype, and collagen gel assay allows to evaluate the influence of eosinophils on ASMC/PF-induced collagen gel shrinkage [18]. Several studies confirmed that collagen gel assay is an appropriate method to evaluate the ASMC and PF contractility in changing environmental conditions such as adding contraction stimulating or inhibiting factors, thus providing a model for tissue contraction [90][91][92][93]. In the current study, we used eosinophils as a contraction of structural lung cells stimulating factor.…”

The Role and Mechanisms of Traditional Chinese Medicine for Airway Inflammation and Remodeling in Asthma: Overview and Progress

“…Other factors such as matrix metalloprotein (MMP), especially MMP-9, MMP-12, or Rho-kinase (ROCK) proteins, contribute to the remodeling process as well by degrading the components of the ECM. Several studies (Bortolozzo et al, 2018;Righetti et al, 2014) using ovalbumin (OVA)-induced models of asthma have shown functional and structural alterations in the respiratory system associated with the high expression of TGF-β, MMP-9, MMP-12 positive cells, and Th2 cytokines: the increased deposition of actin and elastic fibers, and increased mucus production among big and small airways. The functional consequences of these alterations mostly result in the obstruction of small airways, airways narrowing, and the depressing of lung function due to sputum secretion (Ito et al, 2019).…”