scholarly journals A Protective Role of FAM13A in Human Airway Epithelial Cells Upon Exposure to Cigarette Smoke Extract

2021 ◽  
Vol 12 ◽  
Author(s):  
Qing Chen ◽  
Maaike de Vries ◽  
Kingsley Okechukwu Nwozor ◽  
Jacobien A. Noordhoek ◽  
Corry-Anke Brandsma ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cigarette Smoking ◽  
Cigarette Smoke ◽  
Airway Epithelium ◽  
Barrier Function ◽  
Cigarette Smoke Extract ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Copd Patients ◽  
Epithelial Resistance

BackgroundChronic Obstructive Pulmonary Disease (COPD) is a progressive lung disease characterized by chronic inflammation upon inhalation of noxious particles, e.g., cigarette smoke. FAM13A is one of the genes often found to be associated with COPD, however its function in the pathophysiology of COPD is incompletely understood. We studied its role in airway epithelial barrier integrity and cigarette smoke-induced epithelial responses.Materials and MethodsProtein level and localization of FAM13A was assessed with immunohistochemistry in lung tissue from COPD patients and non-COPD controls. In vitro, FAM13A expression was determined in the absence or presence of cigarette smoke extract (CSE) in primary airway epithelial cells (AECs) from COPD patients and controls by western blotting. FAM13A was overexpressed in cell line 16HBE14o- and its effect on barrier function was monitored real-time by electrical resistance. Expression of junctional protein E-cadherin and β-catenin was assessed by western blotting. The secretion of neutrophil attractant CXCL8 upon CSE exposure was measured by ELISA.ResultsFAM13A was strongly expressed in airway epithelium, but significantly weaker in airways of COPD patients compared to non-COPD controls. In COPD-derived AECs, but not those of controls, FAM13A was significantly downregulated by CSE. 16HBE14o- cells overexpressing FAM13A built up epithelial resistance significantly more rapidly, which was accompanied by higher E-cadherin expression and reduced CSE-induced CXCL8 levels.ConclusionOur data indicate that the expression of FAM13A is lower in airway epithelium of COPD patients compared to non-COPD controls. In addition, cigarette smoking selectively downregulates airway epithelial expression of FAM13A in COPD patients. This may have important consequences for the pathophysiology of COPD, as the more rapid build-up of epithelial resistance upon FAM13A overexpression suggests improved (re)constitution of barrier function. The reduced epithelial secretion of CXCL8 upon CSE-induced damage suggests that lower FAM13A expression upon cigarette smoking may facilitate epithelial-driven neutrophilia.

NPS2143 Inhibits MUC5AC and Proinflammatory Mediators in Cigarette Smoke Extract (CSE)-Stimulated Human Airway Epithelial Cells

Inflammation ◽  
2016 ◽  
Vol 40 (1) ◽  
pp. 184-194 ◽  
Author(s):  
Jae-Won Lee ◽  
Ji-Won Park ◽  
Ok-Kyoung Kwon ◽  
Hee Jae Lee ◽  
Hye Gwang Jeong ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cigarette Smoke ◽  
Cigarette Smoke Extract ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Human Airway ◽  
Proinflammatory Mediators ◽  
Human Airway Epithelial Cells

scholarly journals MiR-223 is increased in lungs of patients with COPD and modulates cigarette smoke-induced pulmonary inflammation

2021 ◽  
Author(s):  
Mirjam P. Roffel ◽  
Tania Maes ◽  
Corry-Anke Brandsma ◽  
Maarten van den Berge ◽  
Bart M. Vanaudenaerde ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cigarette Smoke ◽  
Pulmonary Inflammation ◽  
Airway Epithelial Cells ◽  
Negative Regulator ◽  
Stage Ii ◽  
Airway Epithelial ◽  
Copd Patients ◽  
Deficient Mice

Since microRNA (miR)-223-3p modulates inflammatory responses and COPD is associated with amplified pulmonary inflammation, we hypothesized that miR-223-3p plays a role in COPD pathogenesis. Expression of miR-223-3p was measured in lung tissue of 2 independent cohorts with COPD GOLD stage II-IV patients, never smokers and smokers without COPD. The functional role of miR-223-3p was studied in deficient mice and upon overexpression in airway epithelial cells from COPD and controls. We observed higher miR-223-3p levels in patients with COPD stage II-IV compared to (non)-smoking controls, and levels were associated with higher neutrophil numbers in bronchial biopsies of COPD patients. MiR-223-3p expression was also increased in lungs and bronchoalveolar lavage of cigarette smoke (CS)-exposed mice. CS-induced neutrophil and monocyte lung infiltration was stronger in miR-223 deficient mice upon acute (5 days) exposure, but attenuated upon sub-chronic (4 weeks) exposure. Additionally, miR-223 deficiency attenuated acute and sub-chronic CS-induced lung infiltration of dendritic cells and T lymphocytes. Finally, in vitro overexpression of miR-223-3p in non-COPD airway epithelial cells suppressed CXCL8 and GM-CSF secretion and gene expression of the pro-inflammatory transcription factor TRAF6. Importantly, this suppressive effect of miR-223-3p was compromised in COPD-derived cultures. In conclusion, we demonstrate that miR-223-3p is increased in lungs of COPD patients and CS-exposed mice, and is associated with neutrophilic inflammation. In vivo data indicate that miR-223 acts as negative regulator of acute CS-induced neutrophilic and monocytic inflammation. In vitro data suggests that miR-223-3p does so by suppressing pro-inflammatory airway epithelial responses, which is less effective in COPD epithelium.

scholarly journals Sirtuin 3 Inhibits Airway Epithelial Mitochondrial Oxidative Stress in Cigarette Smoke-Induced COPD

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Ming Zhang ◽  
Yeli Zhang ◽  
Michael Roth ◽  
Li Zhang ◽  
Rong Shi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Cigarette Smoke ◽  
Airway Epithelium ◽  
Cell Injury ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Sirtuin 3 ◽  
Mitochondrial Oxidative Stress ◽  
Expression And Activity

Mitochondrial damage in airway epithelial cells plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Sirtuin 3 (Sirt3) is a mitochondrial deacetylase regulating mitochondrial function, but its role in the pathogenesis of COPD is still unknown. The aim of the present study was to investigate the effect of Sirt3 on airway epithelial mitochondria in cigarette smoke-induced COPD. Our present study has shown serious airway inflammation, alveolar space enlargement, and mitochondrial damage of the airway epithelium in COPD rats. Compared to the control rats, Sirt3 protein expression was significantly decreased in the airway epithelium and lung tissue homogenate from COPD rats. In airway epithelial cells (BEAS-2B), cigarette smoke extract (CSE) treatment significantly decreased mRNA and protein expression of Sirt3 and manganese superoxide dismutase (MnSOD), as well as MnSOD activity in a concentration and time-dependent manner. Sirt3 siRNA further significantly intensified the decreases in MnSOD expression and activity and aggravated mitochondrial oxidative stress and cell injury when airway epithelial cells were treated with 7.5% CSE. In contrast, Sirt3 overexpression significantly prevented the decrease of MnSOD expression and activity and improved mitochondrial oxidative stress and cell injury in CSE-treated airway epithelial cells. These data suggest that Sirt3 inhibits airway epithelial mitochondrial oxidative stress possibly through the regulation of MnSOD, thereby contributing to the pathogenesis of COPD.

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