A Mouse Model for Evaluating the Contribution of Fibrocytes and Myofibroblasts to Airway Remodeling in Allergic Asthma

Author(s):  
Matthias Schmidt ◽  
Sabrina Mattoli
2010 ◽  
Vol 156 (6) ◽  
pp. 335-349 ◽  
Author(s):  
Amir A. Zeki ◽  
Jennifer M. Bratt ◽  
Michelle Rabowsky ◽  
Jerold A. Last ◽  
Nicholas J. Kenyon

Author(s):  
S. Pandey ◽  
R. Werner ◽  
N.S. Ambhore ◽  
N.A. Borkar ◽  
S. Bhallamudi ◽  
...  

2015 ◽  
Vol 308 (7) ◽  
pp. L658-L671 ◽  
Author(s):  
Jill R. Johnson ◽  
Erika Folestad ◽  
Jessica E. Rowley ◽  
Elisa M. Noll ◽  
Simone A. Walker ◽  
...  

Myofibroblast accumulation, subepithelial fibrosis, and vascular remodeling are complicating features of chronic asthma, but the mechanisms are not clear. Platelet-derived growth factors (PDGFs) regulate the fate and function of various mesenchymal cells and have been implicated as mediators of lung fibrosis. However, it is not known whether PDGF-BB signaling via PDGFRβ, which is critical for the recruitment of pericytes to blood vessels, plays a role in airway remodeling in chronic asthma. In the present study, we used a selective PDGFRβ inhibitor (CP-673451) to investigate the role of PDGFRβ signaling in the development of airway remodeling and lung dysfunction in an established mouse model of house dust mite-induced chronic allergic asthma. Unexpectedly, we found that pharmacological inhibition of PDGFRβ signaling in the context of chronic aeroallergen exposure led to exacerbated lung dysfunction and airway smooth muscle thickening. Further studies revealed that the inflammatory response to aeroallergen challenge in mice was associated with decreased PDGF-BB expression and the loss of pericytes from the airway microvasculature. In parallel, cells positive for pericyte markers accumulated in the subepithelial region of chronically inflamed airways. This process was exacerbated in animals treated with CP-673451. The results indicate that perturbed PDGF-BB/PDGFRβ signaling and pericyte accumulation in the airway wall may contribute to airway remodeling in chronic allergic asthma.


Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 6
Author(s):  
Soyon Yoon ◽  
Seokcheon Song ◽  
Jae Woo Shin ◽  
Sini Kang ◽  
Hye Young Kim ◽  
...  

The increasing prevalence of allergic asthma has become the world’s major health issue. Current treatments for allergic asthma focus on treating symptoms, while permanent cures still remain undiscovered. In this study, we investigated the effect of Korean traditional herbal remedy, Pyunkang-tang (PGT)—composed of six plants—on asthma alleviation in a mouse model. The PGT mixture was orally gavaged to mice (PM group, 20 mg/mouse/day) from 7 days before sensitization with ovalbumin (OVA) (day −7). On day 0 and day 14, mice from OVA-control (n = 9) and PM group (n = 8) were sensitized with OVA and alum through intraperitoneal injection. On days 18~20, OVA was challenged to mice through nasal injection and sacrificed next day. Cell profile in lung tissue was analyzed by flow cytometry and RT-qPCR analysis, and the number of eosinophils and expression of siglec-F were significantly reduced in the PM group. Lung tissue was examined with hematoxylin and eosin (H&E) and Alcian blue/periodic acid–Schiff (AB-PAS) staining. Noticeably reduced eosinophil infiltration around bronchioles was displayed in the PM group compared to the OVA-control group. Furthermore, PGT-treated mice showed a significant reduction in IL-13 and a mild reduction in IL-5 in lungs. A decreasing tendency of IL-5/13 (+) CD4+ T cells and IL-13(+) innate lymphoid cells (ILCs) and a significant reduction in IL5(+) ILCs were also observed. When treating PGT on murine lung epithelial cells stimulated by papain, there was a significant reduction in IL-33 mRNA expression levels. Taken together, oral delivery of PGT successfully alleviated asthmatic responses provoked by OVA in a mouse model and could lead to novel therapies for allergic asthma.


2017 ◽  
Vol 199 (1) ◽  
pp. 48-61 ◽  
Author(s):  
Carina Klaßen ◽  
Anna Karabinskaya ◽  
Lien Dejager ◽  
Sabine Vettorazzi ◽  
Justine Van Moorleghem ◽  
...  

2003 ◽  
Vol 470 (3) ◽  
pp. 193-199 ◽  
Author(s):  
Joost J. Smit ◽  
Henk Van Loveren ◽  
Maarten O. Hoekstra ◽  
Patrick A.A. Van der Kant ◽  
Gert Folkerts ◽  
...  

Author(s):  
Annelies Bontinck ◽  
Joyceline De Volder ◽  
Mirjam P. Roffel ◽  
Guy G. Brusselle ◽  
Guy F. Joos ◽  
...  
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