Abstract A12: Quercetin inhibits multiple pathways involved in interleukin 6 secretion from human lung fibroblasts and activity in bronchial epithelial cell transformation induced by benzo[a]pyrene diol epoxide

Author(s):  
Wenshu Chen ◽  
Mabel T. Padilla ◽  
Xuling Xu ◽  
Dhimant Desai ◽  
Jacek Krzeminski ◽  
...  
1995 ◽  
Vol 269 (3) ◽  
pp. L377-L387 ◽  
Author(s):  
Y. Nakamura ◽  
L. Tate ◽  
R. F. Ertl ◽  
M. Kawamoto ◽  
T. Mio ◽  
...  

Chronic bronchitis frequently leads to irreversible airway obstruction. Alteration of airway architecture with abnormal airway connective tissue is thought to play an important role in this process. We hypothesized that the epithelial cells that line the airways modulate the development of peribronchial fibrosis and fixed airway obstruction by directing fibroblast proliferation. To assess this, we examined stimulatory activities for human lung fibroblast proliferation in bovine bronchial epithelial cell-conditioned medium. The conditioned medium stimulated the proliferation of fibroblasts in a serum-free culture system in a concentration-dependent manner. The fibroblast growth stimulatory activity was heterogenous, with molecular masses of > 50 and approximately 10 kDa. Bronchial epithelial cell-conditioned medium also contained fibroblast growth inhibitory factors, including both transforming growth factor (TGF)-beta and, based on indomethacin sensitivity, cyclooxygenase products. TGF-beta appeared to contribute to the morphological change of fibroblasts induced by the conditioned medium. Co-culture of human lung fibroblasts with bronchial epithelial cells resulted in a stimulation of fibroblast proliferation. In summary, airway epithelial cells appear to regulate fibroblast proliferation and may play a role in peribronchial fibrosis in chronic bronchitis.


2008 ◽  
Vol 41 (3) ◽  
pp. 393-407 ◽  
Author(s):  
L. Gallelli ◽  
D. Falcone ◽  
G. Pelaia ◽  
T. Renda ◽  
R. Terracciano ◽  
...  

2004 ◽  
Vol 30 (4) ◽  
pp. 585-593 ◽  
Author(s):  
S. Matthew Fitzgerald ◽  
Steven A. Lee ◽  
H. Kenton Hall ◽  
David S. Chi ◽  
Guha Krishnaswamy

2020 ◽  
Vol 177 (1) ◽  
pp. 140-155
Author(s):  
Samantha C Faber ◽  
Nicole A McNabb ◽  
Pablo Ariel ◽  
Emily R Aungst ◽  
Shaun D McCullough

Abstract In vitro bronchial epithelial monoculture models have been pivotal in defining the adverse effects of inhaled toxicant exposures; however, they are only representative of one cellular compartment and may not accurately reflect the effects of exposures on other cell types. Lung fibroblasts exist immediately beneath the bronchial epithelial barrier and play a central role in lung structure and function, as well as disease development and progression. We tested the hypothesis that in vitro exposure of a human bronchial epithelial cell barrier to the model oxidant diesel exhaust particulates caused transepithelial oxidative stress in the underlying lung fibroblasts using a human bronchial epithelial cell and lung fibroblast coculture model. We observed that diesel exhaust particulates caused transepithelial oxidative stress in underlying lung fibroblasts as indicated by intracellular accumulation of the reactive oxygen species hydrogen peroxide, oxidation of the cellular antioxidant glutathione, activation of NRF2, and induction of oxidative stress-responsive genes. Further, targeted antioxidant treatment of lung fibroblasts partially mitigated the oxidative stress response gene expression in adjacent human bronchial epithelial cells during diesel exhaust particulate exposure. This indicates that exposure-induced oxidative stress in the airway extends beyond the bronchial epithelial barrier and that lung fibroblasts are both a target and a mediator of the adverse effects of inhaled chemical exposures despite being separated from the inhaled material by an epithelial barrier. These findings illustrate the value of coculture models and suggest that transepithelial exposure effects should be considered in inhalation toxicology research and testing.


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