Genetic Deletion and Pharmacological Inhibition of PI3K γ Reduces Neutrophilic Airway Inflammation and Lung Damage in Mice with Cystic Fibrosis-Like Lung Disease
Joint Authors
Mall, Marcus
Zhou-Suckow, Zhe
Galluzzo, Maria
Ciraolo, Elisa
Lucattelli, Monica
Hoxha, Eriola
Ulrich, Martina
Campa, Carlo Cosimo
Lungarella, Giuseppe
Doring, Gerd
Hirsch, Emilio
De Rose, Virginia
Source
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-06-21
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Purpose.
Neutrophil-dominated airway inflammation is a key feature of progressive lung damage in cystic fibrosis (CF).
Thus, reducing airway inflammation is a major goal to prevent lung damage in CF.
However, current anti-inflammatory drugs have shown several limits.
PI3Kγ plays a pivotal role in leukocyte recruitment and activation; in the present study we determined the effects of genetic deletion and pharmacologic inhibition of PI3Kγ on airway inflammation and structural lung damage in a mouse model of CF lung disease.
Methods.
βENaC overexpressing mice (βENaC-Tg) were backcrossed with PI3Kγ-deficient ( PI 3 K γ KO ) mice.
Tissue damage was assessed by histology and morphometry and inflammatory cell number was evaluated in bronchoalveolar lavage fluid (BALF).
Furthermore, we assessed the effect of a specific PI3Kγ inhibitor (AS-605240) on inflammatory cell number in BALF.
Results.
Genetic deletion of PI3Kγ decreased neutrophil numbers in BALF of PI 3 K γ KO /βENaC-Tg mice, and this was associated with reduced emphysematous changes.
Treatment with the PI3Kγ inhibitor AS-605240 decreased the number of neutrophils in BALF of βENaC-Tg mice, reproducing the effect observed with genetic deletion of the enzyme.
Conclusions.
These results demonstrate the biological efficacy of both genetic deletion and pharmacological inhibition of PI3Kγ in reducing chronic neutrophilic inflammation in CF-like lung disease in vivo.
American Psychological Association (APA)
Galluzzo, Maria& Ciraolo, Elisa& Lucattelli, Monica& Hoxha, Eriola& Ulrich, Martina& Campa, Carlo Cosimo…[et al.]. 2015. Genetic Deletion and Pharmacological Inhibition of PI3K γ Reduces Neutrophilic Airway Inflammation and Lung Damage in Mice with Cystic Fibrosis-Like Lung Disease. Mediators of Inflammation،Vol. 2015, no. 2015, pp.1-10.
https://search.emarefa.net/detail/BIM-1072417
Modern Language Association (MLA)
Galluzzo, Maria…[et al.]. Genetic Deletion and Pharmacological Inhibition of PI3K γ Reduces Neutrophilic Airway Inflammation and Lung Damage in Mice with Cystic Fibrosis-Like Lung Disease. Mediators of Inflammation No. 2015 (2015), pp.1-10.
https://search.emarefa.net/detail/BIM-1072417
American Medical Association (AMA)
Galluzzo, Maria& Ciraolo, Elisa& Lucattelli, Monica& Hoxha, Eriola& Ulrich, Martina& Campa, Carlo Cosimo…[et al.]. Genetic Deletion and Pharmacological Inhibition of PI3K γ Reduces Neutrophilic Airway Inflammation and Lung Damage in Mice with Cystic Fibrosis-Like Lung Disease. Mediators of Inflammation. 2015. Vol. 2015, no. 2015, pp.1-10.
https://search.emarefa.net/detail/BIM-1072417
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1072417