Kaempferol inhibits endoplasmic reticulum stress‐associated mucus hypersecretion in airway epithelial cells and ovalbumin‐sensitized mice (1045.32)

Abstract Mucus plays an important role in protecting the respiratory tract from irritants. However, mucus hypersecretion is a major indicator of airway diseases. 1,2-Benzisothiazolin-3-one (BIT), as a microbicide, induces asthmatic inflammation. Therefore, we focused on the effects of BIT-related mucin secretion in airway epithelial cells. Our in vivo study showed increased mucus and MUC5AC expressions in the bronchioles of mice that inhaled BIT. For investigating the signaling pathways, we performed experiments in human airway epithelial cells. BIT induced the MUC5AC expression and significantly increased the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). The specific inhibitors of ERK1/2, p38, and NF-κB blocked the BIT-induced MUC5AC expression. Therefore, these results suggest that BIT induces the MUC5AC expression via the ERK1/2, p38, and NF-κB pathways in human airway epithelial cells, which may be involved in mucus hypersecretion associated with airway inflammatory diseases.

Download Full-text

Mechanism of azithromycin in airway diseases

Journal of International Medical Research ◽

10.1177/0300060520932104 ◽

2020 ◽

Vol 48 (6) ◽

pp. 030006052093210

Author(s):

Jie Yang

Keyword(s):

Epithelial Cells ◽

Inflammatory Diseases ◽

Mapk Signaling ◽

Airway Epithelial Cells ◽

Mitogen Activated Protein Kinase ◽

Cell Contact ◽

Airway Epithelial ◽

Mucus Hypersecretion ◽

Chronic Respiratory Diseases ◽

Airway Diseases

Azithromycin (AZM) has been used to treat chronic inflammatory airway diseases because it regulates cell–cell contact between airway epithelial cells. Airway mucus hypersecretion is an important component of chronic respiratory diseases. Mucin 5AC (MUC5AC) is the major mucin produced by airway epithelial cells, and hypersecretion of MUC5AC is a sign of various pulmonary inflammatory diseases. Recently, it was found that matrix metallopeptidase 9 is involved in mucus hypersecretion. Moreover, AZM can inhibit the ability of TNF-α-to induce interleukin (IL)-8 production. This review focuses on the effects on AZM that may be beneficial in inhibiting MUC5AC, matrix metalloprotease-9 and IL-8 production in airway epithelial cells. In addition, recent studies have begun to assess activation of mitogen-activated protein kinase (MAPK) signaling pathways in response to AZM. Understanding these new developments may be helpful for clinicians.

Download Full-text

Azithromycin Inhibits Mucus Hypersecretion from Airway Epithelial Cells

Mediators of Inflammation ◽

10.1155/2012/265714 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 11

Author(s):

Takeshi Shimizu ◽

Shino Shimizu

Keyword(s):

Epithelial Cells ◽

Airway Epithelial Cells ◽

Airway Epithelial ◽

Mucus Hypersecretion

Download Full-text

Brg1 Promotes Airway Mucus Hypersecretion via IL-13 and the JAK1/2-STAT6 Signaling Pathway in Asthma

10.21203/rs.3.rs-1235927/v1 ◽

2022 ◽

Author(s):

Wenjing Zou ◽

maozhu xu ◽

Jie Hu ◽

Lili Yang ◽

Gang Gen ◽

...

Keyword(s):

Epithelial Cells ◽

Signaling Pathway ◽

Periodic Acid ◽

Airway Epithelial Cells ◽

Mucus Secretion ◽

Control Group ◽

Airway Epithelial ◽

Wild Type ◽

Mucus Hypersecretion ◽

Airway Mucus

Abstract Backgroud: The chromatin remodeling factor Brg1 (Brahma-related gene 1) is an important nuclear protein that promotes the transcriptional activation or inhibition of target genes by regulating ATP hydrolysis to generate energy which rearranges the position of nucleosomes and the interaction of histone DNA. In this study, we explored the effect of Brg1 on airway mucus hypersecretion in asthma.Methods: Six-to-eight-week-old female wild-type C57BL/6 mice (wild-type, WT) and type II alveolar epithelial cells (AECIIs) specifically knockout Brg1 mice (Brg1fl/fl) were selected as the experimental subjects. The asthma group was established with house dust mite (HDM), and the control group was treated with normal saline (n=10). Wright's staining was used to detect inflammatory cells in bronchoalveolar lavage fluid (BALF). Invasive lung function was used to assess the airway compliance. Hematoxylin and eosin and periodic acid-schiff staining were used to detect mucus secretion. The virus was used to knock down the Brg1 gene in the bronchial epithelial cell line (16HBE) and stimulated with HDM. Immunohistochemistry was used to measure mucin glycoprotein 5AC (MUC5AC) protein expression in the airway epithelium and 16HBE cells. Western blotting was used to detect the expression of the MUC5AC and JAK1/2-STAT6 signaling pathways in mouse lung tissue and 16HBE. Co-immunoprecipitation (Co-IP) and Chromatin Immunoprecipitation (CHIP) were used to detect whether Brg1 could regulate the JAK1/2-STAT6 signaling pathway.Results: Specifically, knocking out the Brg1 gene in AECIIs can reduce airway inflammation, airway compliance, and mucus hypersecretion in asthma. Knockdown of the Brg1 gene can simultaneously reduce Interleukin-13 (IL-13) and the expression of MUC5AC protein in airway epithelial cells and the activation of the JAK1/2-STAT6 signaling pathway. The results of Co-IP and CHIP showed that Brg1 could bind to the JAK1/2 promoter region, regulating the activity of the JAK1/2-STAT6 pathway affects airway mucus secretion in asthma.Conclusion: Brg1 gene knockout in airway epithelial cells can reduce asthmatic airway mucus hypersecretion and the expression of MUC5AC protein in airway epithelial cells partly by inhibiting the activation of the JAK1/2-STAT6 signaling pathway.

Download Full-text

Cigarette smoke induces MUC5AC mucin overproduction via tumor necrosis factor-α-converting enzyme in human airway epithelial (NCI-H292) cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00019.2004 ◽

2004 ◽

Vol 287 (2) ◽

pp. L420-L427 ◽

Cited By ~ 151

Author(s):

Matt X. G. Shao ◽

Takashi Nakanaga ◽

Jay A. Nadel

Keyword(s):

Epithelial Cells ◽

Cigarette Smoke ◽

Airway Epithelial Cells ◽

Airway Epithelial ◽

Converting Enzyme ◽

Mucus Hypersecretion ◽

Mucin Production ◽

Human Airway ◽

Tnf Α ◽

Factor Α

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death in the U.S. Because cigarette smoking is so importantly implicated in the pathogenesis of COPD and because mucus hypersecretion plays such an important role in COPD, understanding of the mechanisms of smoking-induced mucus hypersecretion could lead to new therapies for COPD. Cigarette smoke causes mucin overproduction via EGF receptor (EGFR) in airway epithelial cells, but the cellular mechanism remains unknown. Airway epithelial cells contain EGFR proligands on their surfaces, which can be cleaved by metalloprotease and subsequently bind to EGFR resulting in mucin production. We hypothesize that TNF-α-converting enzyme (TACE) is activated by cigarette smoke, resulting in increased shedding of EGFR proligand, leading to EGFR phosphorylation and mucin induction in human airway epithelial (NCI-H292) cells. Here we show that cigarette smoke increases MUC5AC production in NCI-H292 cells, an effect that is prevented by an EGFR-neutralizing antibody and by specific knockdown of transforming growth factor-α (TGF-α) using small interfering RNA (siRNA) for TGF-α, implicating TGF-α-dependent EGFR activation in the responses. Cigarette smoke increases TGF-α shedding, EGFR phosphorylation, and mucin production, which are prevented by metalloprotease inhibitors (GM-6001 and TNF-α protease inhibitor-1) and by specific knockdown of TACE with TACE siRNA, implicating TACE in smoking-induced responses. Furthermore, pretreatment with antioxidants prevents smoking-induced TGF-α shedding and mucin production, suggesting that reactive oxygen species is involved in TACE activation. These results implicate TACE in smoking-induced mucin overproduction via the TACE-proligand-EGFR signal pathway in NCI-H292 cells.

Download Full-text