Abstract
Mucus hypersecretion and chronic airway inflammation are standard characteristics of several airway diseases, such as chronic obstructive pulmonary disease and asthma. Increased mucus secretion from increased mucin gene expression in the airway epithelium is associated with poor prognosis and mortality. We previously showed that the absence of tissue inhibitor of metalloproteinase 1 (TIMP-1) enhances lung inflammation, airway hyperreactivity, and lung remodeling in asthma in an ovalbumin (OVA) asthma model of TIMP-1 knockout (TIMPKO) mice as compared to wild-type (WT) controls and mediated by increased galectin-3 (Gal-3) levels. Additionally, we have shown that in the lung epithelial cell line A549, Gal-3 inhibition increases interleukin-17 (IL-17) levels, leading to increased mucin expression in the airway epithelium. Therefore, in the current study, we further examined the relationship between Gal-3 and the production of IL-17-axis cytokines and critical members of the mucin family in the murine TIMPKO asthma model and the lung epithelium cell line A549. While Gal-3 may regulate a Th1/Th2 response, IL-17 could stimulate the mucin genes, MUC5B and MUC5AC. Gal-3 and IL-17 interactions induce mucus expression in OVA-sensitized mice. We conclude that Gal-3 may play an essential role in the pathogenesis of asthma, and modulation of Gal-3 may prove helpful in the treatment of this disease.
Highlights
Mucus hypersecretion and chronic airway inflammation are typical characteristics of obstructive airway diseases, such as chronic obstructive pulmonary disease and asthma [1]
We previously presented that the absence of tissue inhibitor of metalloproteinase 1 (TIMP-1) enhances allergic lung inflammation, airway hyperreactivity (AHR), and lung remodeling in asthma in an ovalbumin (OVA) asthma model of TIMP-1 knockout (TIMPKO) mice compared to wild-type (WT) controls [4]
We observed a significant increase in International Journal of Cell Biology galectin-3 (Gal-3), interleukin-17 (IL-17), and transforming growth factor-β1 (TGF-β1) gene expression in lung tissue isolated from an allergic asthma murine model utilizing TIMPKO
Summary
Mucus hypersecretion and chronic airway inflammation are typical characteristics of obstructive airway diseases, such as chronic obstructive pulmonary disease and asthma [1]. We previously presented that the absence of TIMP-1 enhances allergic lung inflammation, airway hyperreactivity (AHR), and lung remodeling in asthma in an ovalbumin (OVA) asthma model of TIMP-1 knockout (TIMPKO) mice compared to wild-type (WT) controls [4]. We had revealed that a TIMPKO murine allergic asthma model exhibits an asthma phenotype, with airway hyperreactivity, enhanced eosinophilic inflammation, and TH2 cytokine gene and protein expression following sensitization with ovalbumin. We compared the expression of several members of the galectin family and other critical cytokines in a murine allergic asthma model utilizing wild-type and TIMPKO mice [5]. The goal of the current study was to examine the gene and protein expression levels of several key members of the mucin family, namely, MUC5AC and MUC5B, in the lung tissue obtained from the OVAsensitized TIMPKO mice and compare them to levels in the WT controls. We explored the effect of Gal-3 regulation of mucin gene expression using a specific Gal-3 inhibitor peptide (Ac-SDKP) in lung epithelial cells A549 to evaluate mucin gene expression, MUC5B, and MUC5AC
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