scholarly journals TET1 contributes to allergic airway inflammation and regulates interferon and aryl hydrocarbon receptor signaling pathways in bronchial epithelial cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
J. D. Burleson ◽  
Dylan Siniard ◽  
Veda K. Yadagiri ◽  
Xiaoting Chen ◽  
Matthew T. Weirauch ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Aryl Hydrocarbon Receptor ◽  
Airway Inflammation ◽  
Signaling Pathways ◽  
Allergic Airway Inflammation ◽  
Bronchial Epithelial Cells ◽  
Receptor Signaling ◽  
Bronchial Epithelial ◽  
Aryl Hydrocarbon

scholarly journals Epithelial SERPINB10, a novel marker of airway eosinophilia in asthma, contributes to allergic airway inflammation

2019 ◽  
Vol 316 (1) ◽  
pp. L245-L254 ◽  
Author(s):  
Yuqing Mo ◽  
Kan Zhang ◽  
Yuchen Feng ◽  
Lingling Yi ◽  
Yuxia Liang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Airway Inflammation ◽  
Murine Model ◽  
Allergic Airway Inflammation ◽  
Bronchial Epithelial Cells ◽  
Mrna Levels ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Airway Eosinophilia

Serine peptidase inhibitor, clade B, member 10 (SERPINB10) expression is increased in IL-13-stimulated human bronchial epithelial cells and in a murine model of allergic airway inflammation. However, the role of SERPINB10 in asthma remains unknown. We examined the association between epithelial SERPINB10 expression and airway eosinophilia in subjects with asthma and the role of Serpinb10 in allergic airway inflammation in an animal model. Epithelial SERPINB10 mRNA and protein expression were markedly increased in subjects with asthma ( n = 60) compared with healthy controls ( n = 25). Epithelial SERPINB10 mRNA levels were significantly correlated with airway hyperresponsiveness (AHR) and three parameters reflecting airway eosinophilia including the percentage of sputum eosinophils, the number of eosinophils in bronchial submucosa, and fraction of exhaled nitric oxide in subjects with asthma. Moreover, epithelial SERPINB10 expression was strongly correlated with the epithelial gene signature ( CLCA1, POSTN, and SERPINB2) for type 2 status. In normal human bronchial epithelial cells cultured at air-liquid interface, knockdown of SERPINB10 suppressed IL-13-stimulated periostin (encoded by POSTN) and CCL26 (eotaxin-3) expression by inhibiting the activation of p38 MAPK. Epithelial CCL26 mRNA levels were correlated with SERPINB10 expression in subjects with asthma. Airway knockdown of Serpinb10 alleviated AHR, airway eosinophilia and the expression of periostin and Ccl26 in a murine model of allergic airway disease. Taken together, epithelial SERPINB10 is a novel marker for airway eosinophilia in asthma. Epithelial SERPINB10 contributes to allergic airway eosinophilic inflammation, at least in part, by regulating the expression of periostin and CCL26.

Aryl hydrocarbon receptor agonists upregulate VEGF secretion from bronchial epithelial cells

2015 ◽  
Vol 93 (11) ◽  
pp. 1257-1269 ◽  
Author(s):  
Ming-Ju Tsai ◽  
Tsu-Nai Wang ◽  
Yi-Shiuan Lin ◽  
Po-Lin Kuo ◽  
Ya-Ling Hsu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Aryl Hydrocarbon Receptor ◽  
Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Receptor Agonists ◽  
Aryl Hydrocarbon

scholarly journals Lung epithelial CYP1 activity regulates aryl hydrocarbon receptor dependent allergic airway inflammation

2021 ◽  
Author(s):  
Francesca Alessandrini ◽  
Renske de Jong ◽  
Maria Wimmer ◽  
Ann-Marie Maier ◽  
Isis Fernandez ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Aryl Hydrocarbon Receptor ◽  
Airway Inflammation ◽  
Human Lung ◽  
Allergen Challenge ◽  
Allergic Airway Inflammation ◽  
Lung Epithelial Cells ◽  
Aryl Hydrocarbon ◽  
Lung Epithelial ◽  
Cyp1 Family

The lung epithelial barrier serves as a guardian towards environmental insults and responds to allergen encounter with a cascade of immune reactions that can possibly lead to inflammation. Whether the environmental sensor aryl hydrocarbon receptor (AhR) together with its downstream targets cytochrome P450 (CYP1) family members contribute to the regulation of allergic airway inflammation remains unexplored. By employing knockout mice for AhR and for single CYP1 family members, we found that AhR-/- and CYP1B1-/- but not CYP1A1-/- or CYP1A2-/- animals display enhanced allergic airway inflammation compared to WT. Expression analysis, immunofluorescence staining of murine and human lung sections and bone marrow chimeras suggest an important role of CYP1B1 in non-hematopoietic lung epithelial cells to prevent exacerbation of allergic airway inflammation. Transcriptional analysis of murine and human lung epithelial cells indicates a functional link of AhR to barrier protection/inflammatory mediator signaling upon allergen challenge. In contrast, CYP1B1 deficiency leads to enhanced expression and activity of CYP1A1 in lung epithelial cells and to an increased availability of the AhR ligand kynurenic acid following allergen challenge. Thus, differential CYP1 family member expression and signaling via the AhR in epithelial cells represents an immunoregulatory layer protecting the lung from exacerbation of allergic airway inflammation.

Noncanonical role for Ku70/80 in the prevention of allergic airway inflammation via maintenance of airway epithelial cell organelle homeostasis

2020 ◽  
Vol 319 (4) ◽  
pp. L728-L741
Author(s):  
Rakhshinda Rehman ◽  
Vijay Elakkya Vijayakumar ◽  
Ashish Jaiswal ◽  
Vaibhav Jain ◽  
Shravani Mukherjee ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Er Stress ◽  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
Cell Organelle ◽  
Continuous Exposure ◽  
Airway Epithelial ◽  
Bronchial Epithelial ◽  
Ku Proteins

Airway epithelial homeostasis is under constant threat due to continuous exposure to the external environment, and abnormally robust sensitivity to external stimuli is critical to the development of airway diseases, including asthma. Ku is a key nonhomologous end-joining DNA repair protein with diverse cellular functions such as VDJ recombination and telomere length maintenance. Here, we show a novel function of Ku in alleviating features of allergic airway inflammation via the regulation of mitochondrial and endoplasmic reticulum (ER) stress. We first determined that airway epithelial cells derived from both asthmatic lungs and murine asthma models demonstrate increased expression of 8-hydroxy-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage. Ku protein expression was dramatically reduced in the bronchial epithelium of patients with asthma as well as in human bronchial epithelial cells exposed to oxidative stress. Knockdown of Ku70 or Ku80 in naïve mice elicited mitochondrial collapse or ER stress, leading to bronchial epithelial cell apoptosis and spontaneous development of asthma-like features, including airway hyperresponsiveness, airway inflammation, and subepithelial fibrosis. These findings demonstrate an essential noncanonical role for Ku proteins in asthma pathogenesis, likely via maintenance of organelle homeostasis. This novel function of Ku proteins may also be important in other disease processes associated with organelle stress.

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