| First Author | Galluzzo M | Year | 2015 |
| Journal | Mediators Inflamm | Volume | 2015 |
| Pages | 545417 | PubMed ID | 26185363 |
| Mgi Jnum | J:233536 | Mgi Id | MGI:5784943 |
| Doi | 10.1155/2015/545417 | Citation | Galluzzo M, et al. (2015) Genetic Deletion and Pharmacological Inhibition of PI3K gamma Reduces Neutrophilic Airway Inflammation and Lung Damage in Mice with Cystic Fibrosis-Like Lung Disease. Mediators Inflamm 2015:545417 |
| abstractText | 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. PI3Kgamma plays a pivotal role in leukocyte recruitment and activation; in the present study we determined the effects of genetic deletion and pharmacologic inhibition of PI3Kgamma on airway inflammation and structural lung damage in a mouse model of CF lung disease. METHODS: betaENaC overexpressing mice (betaENaC-Tg) were backcrossed with PI3Kgamma-deficient (PI3Kgamma (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 PI3Kgamma inhibitor (AS-605240) on inflammatory cell number in BALF. RESULTS: Genetic deletion of PI3Kgamma decreased neutrophil numbers in BALF of PI3Kgamma (KO)/betaENaC-Tg mice, and this was associated with reduced emphysematous changes. Treatment with the PI3Kgamma inhibitor AS-605240 decreased the number of neutrophils in BALF of betaENaC-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 PI3Kgamma in reducing chronic neutrophilic inflammation in CF-like lung disease in vivo. |
