Endoplasmic reticulum stress in airway hyperresponsiveness

Duan, Qirui; Zhou, Ying; Yang, Dong

doi:10.1016/j.biopha.2022.112904

Cited by 9 publications

(5 citation statements)

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“…The IRE1α pathway may be more crucial in promoting PM2.5-induced ER stress. The results of a previous study confirmed that IRE1α promoted NF-κB by increasing X-box-binding protein 1, which plays a key role in the inflammatory response of airway epithelial cells (46). The results of the present study demonstrated that ATF6, PERK and IRE1α exert specific regulatory effects on PM2.5-induced apoptosis and the overproduction of ROS, IL-6, TNF-α and MUC5AC; however, IRE1α exhibited a greater regulatory potential.…”

Section: Discussionsupporting

confidence: 86%

Fine particulate matter promotes airway inflammation and mucin production by activating endoplasmic reticulum stress and the IRE1α/NOD1/NF‑κB pathway

Hu,

Xu,

Tang

et al. 2023

Int J Mol Med

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Fine particulate matter (PM2.5) is a type of small particle that is <2.5 μ m in diameter that may cause airway inflammation. Thus, the present study aimed to explore the effects of PM2.5 on endoplasmic reticulum (ER) stress and airway inflammation in human airway epithelial cells. For this purpose, HBE135-E6E7 airway epithelial cells were cultured and exposed to specific concentrations of PM2.5 for various periods of time, and cell viability was determined using a Cell Counting Kit-8 assay. The results of the present study demonstrated that exposure to PM2.5 increased the mRNA and protein expression levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α and mucin 5AC (MUC5AC). Moreover, the expression levels of ER stress-related proteins, such as glucose-regulated protein 78, CCAAT-enhancer binding protein homologous protein, activating transcription factor 6, protein kinase R-like ER kinase (PERK), phosphorylated (p-)PERK, inositol-requiring enzyme 1α (IRE1α) and p-IRE1α, and nucleotide-binding oligomerization domain 1 (NOD1) expression levels were increased following exposure to PM2.5. Transfection with IRE1α small interfering RNA (siRNA) led to the increased production of IL-6, TNF-α and MUC5AC. Moreover, the expression of NOD1 and the translocation of NF-κB p65 were inhibited following transfection with IRE1α siRNA. In addition, the results of the present study demonstrated that transfection with NOD1 siRNA decreased the production of IL-6, TNF-α and MUC5AC, and decreased the translocation of NF-κB p65. The expression levels of IL-6, TNF-α and MUC5AC were increased in the HBE135-E6E7 cells following treatment with C12-iE-DAP, a NOD1 agonist. Moreover, treatment with C12-iE-DAP led to the activation of NF-κB p65. Collectively, the results of the present study suggest that PM2.5 promotes airway inflammation and mucin production by activating ER stress in HBE135-E6E7 airway epithelial cells, and that the IRE1α/NOD1/NF-κB pathway may be involved in this process.

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Section: Discussionsupporting

confidence: 86%

Fine particulate matter promotes airway inflammation and mucin production by activating endoplasmic reticulum stress and the IRE1α/NOD1/NF‑κB pathway

Hu,

Xu,

Tang

et al. 2023

Int J Mol Med

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“…Airway Hyperresponsiveness: Airway hyperresponsiveness refers to an exaggerated sensitivity of the airways to stimuli, such as allergens or irritants, resulting in bronchospasm and constriction. It is a crucial clinical feature in pulmonary diseases (allergic rhinitis, asthma, COPD) and is closely related to airway inflammation, remodeling, and mucus secretion, playing a significant role in the progression of UAD ( 42 , 43 ).…”

Section: Discussionmentioning

confidence: 99%

Causal associations between pediatric asthma and united airways disease: a two-sample Mendelian randomization analysis

Gao,

Cai,

et al. 2024

Front. Med.

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BackgroundPrior observational research has indicated a potential link between pediatric asthma and united airways disease (UAD). However, these findings could be subject to confounding factors and reverse causation. Therefore, our study utilizes Mendelian randomization (MR) method to further investigate the causal relationship between pediatric asthma and UAD.MethodsWe conducted a comprehensive two-sample Mendelian randomization (MR) analysis to investigate the association between pediatric asthma and seven groups of UAD, including chronic sinusitis, chronic rhinitis, nasopharyngitis and pharyngitis, chronic diseases of tonsils and adenoids, chronic laryngitis and laryngotracheitis, chronic bronchitis, bronchiectasis, chronic obstructive pulmonary disease (COPD). The present study employed a range of methods for two-sample MR analysis, including inverse variance weighted (IVW), MR-Egger regression, Simple mode, weighted median, and weighted models. The conclusion of the MR analysis primarily relies on the IVW results, while other analytical methods are utilized as supplementary evidence to ensure result robustness in this MR analysis. And sensitivity analyses were conducted, including heterogeneity test, horizontal pleiotropy test, MR-PRESSO test, and leave-one-out analysis to validate the results.ResultsThe results of the MR analysis indicate significant causal effects of pediatric asthma on chronic rhinitis, nasopharyngitis and pharyngitis (IVW: OR = 1.15, 95%CI: 1.05–1.26, p-value = 0.003), chronic diseases of tonsils and adenoids (IVW: OR = 1.07, 95%CI: 1.00–1.15, p-value = 0.038), chronic bronchitis (IVW: OR = 1.51, 95%CI: 1.42–1.62, p-value <0.001), bronchiectasis (IVW: OR = 1.51, 95%CI: (1.30–1.75), p-value <0.001), and COPD (IVW: OR = 1.43, 95%CI: 1.34–1.51, p-value <0.001). However, no significant causal association was observed between pediatric asthma and chronic sinusitis (IVW: OR = 1.00, 95%CI: 1.00–1.00, p-value = 0.085), chronic laryngitis and laryngotracheitis (IVW: OR = 1.05, 95%CI: 0.90–1.21, p-value = 0.558).ConclusionOur findings support a potential causal relationship between pediatric asthma and UAD, suggesting that pediatric asthma may be a potential risk factor for various UAD.

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“…The hypertonic saline has been proved to have no effect on cell counts of sputum in healthy and asthmatic patients ( Belda et al, 2005 ). Mch interacts with muscarinic receptors to induce AHR while inflammation cells interact with pattern recognition receptors and then mediate NF-κB to trigger AHR ( Coates et al, 2017 ; Duan et al, 2022 ). We tested bronchoalveolar lavage fluid in an ovalbumin-induced asthma model, showing no effects on inflammatory cells after Mch inhalation ( Supplementary Figure S3 ).…”

Section: Discussionmentioning

confidence: 99%

The Effects of a Transgelin-2 Agonist Administered at Different Times in a Mouse Model of Airway Hyperresponsiveness

et al. 2022

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Airway hyperresponsiveness (AHR) is one of the most important features of asthma. Our previous study showed that inhaled transgelin-2 agonist, TSG12, effectively reduced pulmonary resistance in a mouse model of asthma in a dose-dependent manner. However, the optimal administration time of TSG12 to reduce AHR and the pharmacological effects are still unclear. In this study, the effects of TSG12 inhalation before and during AHR occurrence were examined. The results showed that the pulmonary resistance was reduced by 57% and the dynamic compliance was increased by 46% in the TSG12 Mch group (atomize TSG12 10 min before methacholine, p < 0.05 vs. model). The pulmonary resistance was reduced by 61% and the dynamic compliance was increased by 47% in the TSG12 + Mch group (atomize TSG12 and methacholine together, p < 0.05 vs. model). Quantitative real-time PCR showed that the gene expression levels of transgelin-2, myosin phosphatase target subunit-1, and myosin light chain were up-regulated by 6.4-, 1.9-, and 2.8-fold, respectively, in the TSG12 Mch group. The gene expression levels of transgelin-2, myosin phosphatase target subunit-1, and myosin light chain were up-regulated by 3.2-, 1.4-, and 1.9-fold, respectively, in the TSG12 + Mch group. The results suggested that TSG12 effectively reduces pulmonary resistance when TSG12 inhalation occurred both before and during AHR occurrence. Gene expression levels of transgelin-2 and myosin light chain were significantly up-regulated when TSG12 inhalation occurred before AHR occurrence. This study may provide a basis for the administration time of TSG12 for asthma treatment in the future.

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Endoplasmic reticulum stress in airway hyperresponsiveness

Cited by 9 publications

References 80 publications

Fine particulate matter promotes airway inflammation and mucin production by activating endoplasmic reticulum stress and the IRE1α/NOD1/NF‑κB pathway

Fine particulate matter promotes airway inflammation and mucin production by activating endoplasmic reticulum stress and the IRE1α/NOD1/NF‑κB pathway

Causal associations between pediatric asthma and united airways disease: a two-sample Mendelian randomization analysis

The Effects of a Transgelin-2 Agonist Administered at Different Times in a Mouse Model of Airway Hyperresponsiveness

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