Influences of PON1 on airway inflammation and remodeling in bronchial asthma

Abstract

This study aims to explore the influences of Paraoxonase-1 (PON1) involved in airway inflammation and remodeling in asthma. Mice were divided into control, asthma, asthma + PON1 and asthma + NC groups, and asthma models were established via aerosol inhalation of ovalbumin (OVA). HE, Masson, and PAS stains were used to observe airway inflammation and remodeling, Giemsa staining to assess inflammatory cells in bronchoalveolar lavage fluid (BALF), qRT-PCR and Western blot to detect PON1 expression, lipid peroxidation and glutathione assays to quantify malondialdehyde (MDA) activity and glutathione peroxidase (GSH) levels, ELISA to determine inflammatory cytokines and immunoglobulin, and colorimetry to detect PON1 activities. Additionally, mice lung macrophages and fibroblasts were transfected with PON1 plasmid in vitro; ELISA and qRT-PCR were performed to understand the effects of PON1 on inflammatory cytokines secreted by lung macrophages, MTT assay for lung fibroblasts proliferation and qRT-PCR and Western blot for the expressions of PON1, COL1A1, and fibronectin. After overexpression of PON1, the asthma mice had decreased inflammatory cell infiltration, fibrosis degree, and airway wall thickness; inflammatory cells and inflammatory cytokines in BALF were also reduced, expressions of OVA-IgE and IgG1, and MDA activity were decreased, but the expressions of OVA-IgG2a and INF-γ and GSH levels were increased. Besides, PON1 significantly inhibited microphage expression of LPS-induced inflammatory cytokines, lung fibroblast proliferation, and COL1A1 and fibronectin expression.Thus, PON1 could relieve airway inflammation and airway remodeling in asthmatic mice and inhibit the secretion of LPS-induced macrophage inflammatory cytokines and the proliferation of lung fibroblasts. K E Y W O R D Sairway inflammation, airway remodeling, asthma, paraoxonase-1

Ferret models of alpha-1 antitrypsin deficiency develop lung and liver disease

“…A notable finding within our BAL proteomics was that paraoxonase-1 (PON1) was 300-fold lower in AAT-KO ferret BAL than in controls ( Figure 5E ). This protein has been observed to be reduced in an ovalbumin-induced model of asthma where overexpression was associated with improved airway inflammatory state and limited remodeling ( 44 ). Moreover, expression of PON1 is protective against pseudomonal infection ( 45 ), which suggests that downregulation of PON1 in the BAL of AAT-KO ferrets may be of interest in future studies of airway infection.…”

“…A notable finding within our BAL proteomics was that paraoxonase-1 (PON1) was 300-fold lower in AAT-KO ferret BAL than in controls (Figure 5E). This protein has been observed to be reduced in an ovalbumin-induced model of asthma where overexpression was associated with improved airway inflammatory state and limited remodeling (44).…”

Screening and Functional Pathway Analysis of Pulmonary Genes Associated with Suppression of Allergic Airway Inflammation by Adipose Stem Cell-Derived Extracellular Vesicles

“…Recent studies have shown that PON1 expression and activity were significantly decreased in asthma and may have potential effects on asthma diagnosis [ 35 , 41 , 42 ]. Furthermore, PON1 decreased airway inflammation and airway remodeling in asthmatic mice and inhibited macrophage expression of LPS-induced inflammatory cytokines and lung fibroblast proliferation [ 43 ]. Bex2 regulates mitochondrial apoptosis and the G1 cell cycle in breast cancer [ 44 ].…”

The Role of Oxidative Stress in Sarcoidosis

“…In the lung, PON1 has been detected through immunohistochemical evidence in type 1 pneumocytes, but its physiological role in the context of lung antioxidant activity has not yet been described [ 97 ]. However, there are a few publications on the role of PON1 activity in patients with asthma and COPD [ 98 , 99 , 100 ] and on its impact on lung cancer behavior and progression by antioxidative function and controlled ROS accumulation [ 101 ].…”