scholarly journals The PPAR-γ agonist pioglitazone exerts proinflammatory effects in bronchial epithelial cells during acute Pseudomonas aeruginosa pneumonia

2022 ◽  
Author(s):  
Bianca L Ferreira ◽  
Ivan Ramirez-Moral ◽  
Natasja A Otto ◽  
Reinaldo Salomão ◽  
Alex F de Vos ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Airway Inflammation ◽  
Inflammatory Responses ◽  
Tricarboxylic Acid Cycle ◽  
Bronchial Epithelial Cells ◽  
Respiratory Pathogen ◽  
Peroxisome Proliferator ◽  
Bronchial Epithelial ◽  
Ppar Γ ◽  
Proinflammatory Effect

Abstract Pseudomonas (P.) aeruginosa is a common respiratory pathogen that causes injurious airway inflammation during acute pneumonia. PPAR (peroxisome proliferator-activated receptor)-γ is involved in the regulation of metabolic and inflammatory responses in different cell types and synthetic agonists of PPAR-γ exert anti-inflammatory effects on myeloid cells in vitro and in models of inflammation in vivo. We sought to determine the effect of the PPAR-γ agonist pioglitazone on airway inflammation induced by acute P. aeruginosa pneumonia, focusing on bronchial epithelial cells. Mice pretreated with pioglitazone or vehicle (-24 and -1 hour) were infected with P. aeruginosa via the airways. Pioglitazone treatment was associated with increased expression of chemokine (Cxcl1, Cxcl2, Ccl20) and cytokine genes (Tnfa, Il6, Cfs3) in bronchial brushes obtained 6 hours after infection. This proinflammatory effect was accompanied by increased expression of Hk2 and Pfkfb3, genes encoding rate limiting enzymes of glycolysis; concurrently, the expression of Sdha, important for maintaining metabolite flux in the tricarboxylic acid cycle, was reduced in bronchial epithelial cells of pioglitazone treated-mice. Pioglitazone inhibited bronchoalveolar inflammatory responses measured in lavage fluid. These results suggest that pioglitazone exerts a selective proinflammatory effect on bronchial epithelial cells during acute P. aeruginosa pneumonia, possibly by enhancing intracellular glycolysis.

scholarly journals p120 Modulates LPS-Induced NF-κB Activation Partially through RhoA in Bronchial Epithelial Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Lingzhi Qin ◽  
Shenghui Qin ◽  
Yanli Zhang ◽  
Chao Zhang ◽  
Heng Ma ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Airway Inflammation ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Adherens Junction ◽  
Bronchial Epithelial Cells ◽  
Rock Inhibitor ◽  
Bronchial Epithelial ◽  
Rhoa Activity ◽  
Junction Protein

p120-Catenin (p120) is an adherens junction protein recognized to regulate cell-cell adhesion. Emerging evidence indicates that p120 may also play an important role in inflammatory responses, and the regulatory mechanisms are still unknown. In the present study, we showed that p120 was associated with airway inflammation. p120 downregulation induced nuclear factor-κB (NF-κB) activation, accompanied with IκBαdegradation, p65 nuclear translocation, and increased expression of interleukin-8 (IL-8) in lipopolysaccharide (LPS)- treated C57BL mice and human bronchial epithelial cells (BECs). Moreover, we first found that p120 directly coprecipitated with RhoA in BECs. After LPS stimulation, although total RhoA and p120-bound RhoA were unchanged, RhoA activity was increased. Y27632, a ROCK inhibitor, could partially inhibit nuclear translocation of p65. Overexpression of p120 inactivated RhoA and NF-κB in BECs, whereas p120 loss significantly increased RhoA activity, p65 nuclear translocation, and IL-8 expression. Taken together, our study supports the regulatory role of p120 in airway inflammation and reveals that p120 may modulate NF-κB signaling partially through RhoA.

scholarly journals Haemophilus influenzae causes cellular trans-differentiation in human bronchial epithelia

2021 ◽  
Vol 27 (3) ◽  
pp. 251-259
Author(s):  
Michael Glöckner ◽  
Sebastian Marwitz ◽  
Kristina Rohmann ◽  
Henrik Watz ◽  
Dörte Nitschkowski ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Haemophilus Influenzae ◽  
Bronchial Epithelium ◽  
Bronchial Epithelial Cells ◽  
Respiratory Pathogen ◽  
Chronic Obstructive ◽  
Bronchial Epithelial ◽  
Extracellular Matrix Components ◽  
The Impact ◽  
Primary Bronchial Epithelial Cells

Non-typeable Haemophilus influenzae (NTHi) is the most common respiratory pathogen in patients with chronic obstructive disease. Limited data is available investigating the impact of NTHi infections on cellular re-differentiation processes in the bronchial mucosa. The aim of this study was to assess the effects of stimulation with NTHi on the bronchial epithelium regarding cellular re-differentiation processes using primary bronchial epithelial cells harvested from infection-free patients undergoing bronchoscopy. The cells were then cultivated using an air-liquid interface and stimulated with NTHi and TGF-β. Markers of epithelial and mesenchymal cells were analyzed using immunofluorescence, Western blot and qRT-PCR. Stimulation with both NTHi and TGF-ß led to a marked increase in the expression of the mesenchymal marker vimentin, while E-cadherin as an epithelial marker maintained a stable expression throughout the experiments. Furthermore, expression of collagen 4 and the matrix-metallopeptidases 2 and 9 were increased after stimulation, while the expression of tissue inhibitors of metallopeptidases was not affected by pathogen stimulation. In this study we show a direct pathogen-induced trans-differentiation of primary bronchial epithelial cells resulting in a co-localization of epithelial and mesenchymal markers and an up-regulation of extracellular matrix components.

scholarly journals A Tissue-Engineered Tracheobronchial In Vitro Co-Culture Model for Determining Epithelial Toxicological and Inflammatory Responses

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 631
Author(s):  
Luis Soriano ◽  
Tehreem Khalid ◽  
Fergal J. O'Brien ◽  
Cian O'Leary ◽  
Sally-Ann Cryan
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Responses ◽  
Bronchial Epithelial Cells ◽  
Lung Fibroblasts ◽  
Drug Induced ◽  
Bronchial Epithelial ◽  
Culture Model ◽  
Epithelial Cultures

Translation of novel inhalable therapies for respiratory diseases is hampered due to the lack of in vitro cell models that reflect the complexity of native tissue, resulting in many novel drugs and formulations failing to progress beyond preclinical assessments. The development of physiologically-representative tracheobronchial tissue analogues has the potential to improve the translation of new treatments by more accurately reflecting in vivo respiratory pharmacological and toxicological responses. Herein, advanced tissue-engineered collagen hyaluronic acid bilayered scaffolds (CHyA-B) previously developed within our group were used to evaluate bacterial and drug-induced toxicity and inflammation for the first time. Calu-3 bronchial epithelial cells and Wi38 lung fibroblasts were grown on either CHyA-B scaffolds (3D) or Transwell® inserts (2D) under air liquid interface (ALI) conditions. Toxicological and inflammatory responses from epithelial monocultures and co-cultures grown in 2D or 3D were compared, using lipopolysaccharide (LPS) and bleomycin challenges to induce bacterial and drug responses in vitro. The 3D in vitro model exhibited significant epithelial barrier formation that was maintained upon introduction of co-culture conditions. Barrier integrity showed differential recovery in CHyA-B and Transwell® epithelial cultures. Basolateral secretion of pro-inflammatory cytokines to bacterial challenge was found to be higher from cells grown in 3D compared to 2D. In addition, higher cytotoxicity and increased basolateral levels of cytokines were detected when epithelial cultures grown in 3D were challenged with bleomycin. CHyA-B scaffolds support the growth and differentiation of bronchial epithelial cells in a 3D co-culture model with different transepithelial resistance in comparison to the same co-cultures grown on Transwell® inserts. Epithelial cultures in an extracellular matrix like environment show distinct responses in cytokine release and metabolic activity compared to 2D polarised models, which better mimic in vivo response to toxic and inflammatory stimuli offering an innovative in vitro platform for respiratory drug development.

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