scholarly journals Deletion of Shp2 in bronchial epithelial cells impairs IL-25 production in vitro, but has minor influence on asthmatic inflammation in vivo

PLoS ONE ◽  
2017 ◽  
Vol 12 (5) ◽  
pp. e0177334
Author(s):  
Zhangwei Qiu ◽  
Jiesen Zhou ◽  
Fang Liu ◽  
Xuejun Qin ◽  
Yuanrong Dai ◽  
...  
2012 ◽  
Vol 130 (6) ◽  
pp. 1375-1383 ◽  
Author(s):  
Jin-Ah Park ◽  
Asma S. Sharif ◽  
Daniel J. Tschumperlin ◽  
Laurie Lau ◽  
Rachel Limbrey ◽  
...  

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 631
Author(s):  
Luis Soriano ◽  
Tehreem Khalid ◽  
Fergal J. O'Brien ◽  
Cian O'Leary ◽  
Sally-Ann Cryan

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.


1996 ◽  
Vol 5 (3) ◽  
pp. 210-217
Author(s):  
M. M. Verheggen ◽  
H. I. M. de Bont ◽  
P. W. C. Adriaansen-Soeting ◽  
B. J. A. Goense ◽  
C. J. A. M. Tak ◽  
...  

In this study, we investigated the expression of lipocortin I and II (annexin I and I in the human bronchial epithelium, bothin vivoandin vitro. A clear expression of lipocortin I and II protein was found in the epithelium in sections of bronchial tissue. In cultured human bronchial epithelial cells we demonstrated the expression of lipocortin I and II mRNA and protein using Northern blotting, FACScan analysis and ELISA. No induction of lipocortin I or II mRNA or protein was observed after incubation with dexamethasone. Stimulation of bronchial epithelial cells with IL-1β, TNF-α or LPS for 24 h did not affect the lipocortin I or II mRNA or protein expression, although PGE2and 6-keto-PGF1αproduction was significantly increased. This IL-1β- and LPS-mediated increase in eicosanoids could be reduced by dexamethasone, but was not accompanied by an increase in lipocortin I or II expression. In human bronchial epithelial cells this particular glucocorticoid action is not mediated through lipocortin I or II induction.


Lung ◽  
1997 ◽  
Vol 175 (5) ◽  
pp. 287-298 ◽  
Author(s):  
A. T. Hastie ◽  
K. B. Everts ◽  
J. R. Shaver ◽  
R. Cirelli ◽  
J. Zangrilli ◽  
...  

Author(s):  
Maximillian Woodall ◽  
Boris Reidel ◽  
Mehmet Kesimer ◽  
Robert Tarran ◽  
Deborah L Baines

Airway secretions contain many signalling molecules and peptides/proteins that are not found in airway surface liquid (ASL) generated by normal human bronchial epithelial cells (NHBE) in vitro. These play a key role in innate defence and mediate communication between the epithelium, immune cells and the external environment. We investigated how culture of NHBE with apically applied secretions from healthy or disease (Cystic Fibrosis, CF) lungs affected epithelial function with a view to providing better in vitro models of the in vivo environment. NHBE from 6-8 different donors were cultured at air-liquid interface (ALI), with apically applied sputum from normal healthy donors (NLS) or CF donors (CFS) for 2-4 hours, 48 hours or with sputum reapplied over 48 hours. Proteomic analysis was carried out on the sputa and on NHBE ASL before and after culture with sputa. Transepithelial electrical resistance (TEER), short circuit current (Isc) and changes to ASL height were measured. There were 71 proteins common to both sputa but not ASL. The protease:protease inhibitor balance was increased in CFS compared to NLS and ASL. Culture of NHBE with sputa for 48 hours identified additional factors not present in NLS, CFS or ASL alone. Culture with either NLS or CFS for 48 hours increased CFTR activity, calcium activated chloride channel (CaCC) activity and changed ASL height. These data indicate that culture with healthy or disease sputum changes the proteomic profile of ASL and ion transport properties of NHBE and this may increase physiological relevance when using in vitro airway models.


2016 ◽  
Vol 310 (1) ◽  
pp. L59-L70 ◽  
Author(s):  
Mark J. Turner ◽  
Elizabeth Matthes ◽  
Arnaud Billet ◽  
Amy J. Ferguson ◽  
David Y. Thomas ◽  
...  

Cystic fibrosis (CF), a genetic disease caused by mutations in the CFTR gene, is a life-limiting disease characterized by chronic bacterial airway infection and severe inflammation. Some CFTR mutants have reduced responsiveness to cAMP/PKA signaling; hence, pharmacological agents that elevate intracellular cAMP are potentially useful for the treatment of CF. By inhibiting cAMP breakdown, phosphodiesterase (PDE) inhibitors stimulate CFTR in vitro and in vivo. Here, we demonstrate that PDE inhibition by RPL554, a drug that has been shown to cause bronchodilation in asthma and chronic obstructive pulmonary disease (COPD) patients, stimulates CFTR-dependent ion secretion across bronchial epithelial cells isolated from patients carrying the R117H/ F508del CF genotype. RPL554-induced CFTR activity was further increased by the potentiator VX-770, suggesting an additional benefit by the drug combination. RPL554 also increased cilia beat frequency in primary human bronchial epithelial cells. The results indicate RPL554 may increase mucociliary clearance through stimulation of CFTR and increasing ciliary beat frequency and thus could provide a novel therapeutic option for CF.


2002 ◽  
Vol 10 (1) ◽  
pp. 31-40 ◽  
Author(s):  
Neil R. Mathias ◽  
Julita Timoszyk ◽  
Paul I. Stetsko ◽  
John R. Megill ◽  
Ronald L. Smith ◽  
...  

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