Cytoprotective Effect of Kaempferol on Paraquat-Exposed BEAS-2B Cells <i>via</i> Modulating Expression of <i>MUC5AC</i>

Abstract

Mucins are highly glycosylated secretary proteins produced by most epithelial cells. Hypersecretion of mucins is one of the prominent symptoms of several airway diseases, including asthma, cystic fibrosis, nasal allergy, rhinitis, and sinusitis. Paraquat (PQ), a common herbicide, has been associated with pulmonary damage and is a potent reactive oxygen species (ROS) producer. However, until now the role of PQ on mucin overproduction has not been studied. The aim of this study is to explore how kaempferol (KM), a widely used dietary flavonoid, affects the protection of human PQ-exposed bronchial epithelium BEAS-2B cells by suppressing Mucin gene expression via nuclear factor-kappa B (NF-κB). We observed that PQ generates intracellular ROS, and also induces lipid peroxidation in BEAS-2B cells. Additionally, we found that PQ effectively induces the expression of the MUC5AC gene; however, co-treatment of PQ with KM drastically reduces its expression. Furthermore, we observed that PQ activates NF-κB, while co-treatment with KM occludes its nuclear translocation, and additionally KM repressed the PQ phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) in BEAS-2B cells. Based on our data, we believe that KM can suppress the over-expression of the MUC5AC gene. This would contribute to the protection of PQ cytotoxicity to exposed BEAS-2B cells, and allow further study toward a better understanding of ROSassociated diseases.Key words MUC5AC; kaempferol; reactive oxygen species; human bronchial epithelial BEAS-2B cell; nuclear factor-kappa B Several studies have been carried out demonstrating hypersecretion of mucous from respiratory epithelial cells a major pathological event in chronic airway diseases such as chronic obstructive pulmonary diseases or asthma.1,2) These pathological manifestations are governed by the interaction between underlying genetic factors and xenobiotics, which together are responsible for intercellular reactive oxygen species (ROS) production.3) Findings have shown that ROS such as: hydrogen peroxide, superoxide anion, hydroxyl ion are responsible for the initiation and progression of chronic airway diseases via over-expression of Mucin genes.4-6) ROS is a major etiological factor in the pathogenesis of chronic inflammatory airway diseases as it triggers mucin secretion in epithelia. 7)Twenty different MUC genes have been characterized in human airway epithelia, these are then subdivided into membrane-bound and secreted forms.8-11) MUC5AC is a hallmark gene, and considered the most phenotypical gene in respiratory diseases; it accumulates in respiratory tract can lead to symptoms such as chronic cough and excessive sputum production. Previous studies showed that paraquat (PQ) is a potent ROS inducer in different epithelial cell lines [12][13][14] and is associated with cellular cytoxicity. However, there has been no study into whether PQ can induce MUC gene expression or not, so in this study we investigated the effects of PQ on Bronchial epithelial BEAS...

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“…Furthermore, kaempferol affects protection from the human Paraquat (PQ)‐exposed bronchial epithelium BEAS‐2B cells by inhibiting mucin gene expression via NF‐κB. It additionally suppresses the PQ phosphorylation of ERK and c‐JNK (Podder, Song, Song, & Kim, ). In BEAS‐2B cells of BALB/c mice, kaempferol suppressed the lipopolysaccharide (LPS)‐induced bronchial EMT.…”

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