Background: Phosphoinositide 3-kinase (PI3K) plays an important role in tissue inflammatory reactions and fibrotic processes. The objective of this study was to evaluate the potential mechanism and therapeutic effects of PI3K inhibitor on pancreatic elastase (PE)-induced acute and chronic lung inflammation, edema, and injury.
Methods: Rats were terminated at 7 or 28 days after an intratracheal challenge with PE and intranasal instillation with a PI3K inhibitor, SHBM1009. Alterations of airway epithelial cells and myofibroblasts were studied in vitro.
Measurements: Lung inflammation, edema, and injury; emphysema; and tissue remodeling were measured after PE instillation with or without treatment with PI3K inhibitor and budesonide. Cellular biologic functions were monitored.
Results: SHBM1009 could prevent PE-induced acute lung inflammation, edema, and injury, and chronic lung inflammation, remodeling, and emphysema. Different patterns of inhibitory effects of SHBM1009 and BEZ235, a dual PI3K/mechanistic target of rapamycin inhibitor, on PE-challenged epithelial cells were observed. PE per se reduced epithelial cell proliferation and stability through the inhibition of cell division rather than promoting cell death, in dose- and time-dependent patterns. Effects of PI3K inhibitors on cells were associated with the severity of PE challenges.
Conclusions: PI3K plays a critical role in the development of acute and chronic lung injury, including the process of tissue remodeling and emphysema. PI3K inhibitors could be new therapeutic alternatives for chronic lung diseases.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1378/chest.12-1040 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Rupture of the staple suture site after stapling the right inferior pulmonary vein with double rows of staples: a case report.
Gen Thorac Cardiovasc Surg Cases
January 2025
Department of Surgery II, Faculty of Medicine, Yamagata University, Yamagata, Japan.
Background: With advancements in minimally invasive thoracic surgery techniques, such as video-assisted thoracoscopic surgery and robotic surgery, the design of vascular staplers has evolved to meet the requirements of these procedures. Consequently, newer generations of automatic staplers with improved handling and reduced size have been introduced, such as two-row staplers, which are more maneuverable and less bulky than their three-row counterparts.
Case Presentation: A 68-year-old man with lung cancer underwent a right middle and lower lobectomy due to tumor invasion into the central middle bronchial trunk, rendering the preservation of the middle lobe impossible.
An integrated investigation of mitochondrial genes in COPD reveals the causal effect of NDUFS2 by regulating pulmonary macrophages.
Biol Direct
January 2025
Key Laboratory of Geriatrics of Jiangsu Province, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.
Background: Despite the increasing body of evidence that mitochondrial activities implicate in chronic obstructive pulmonary disease (COPD), we are still far from a causal-logical and mechanistic understanding of the mitochondrial malfunctions in COPD pathogenesis.
Results: Differential expression genes (DEGs) from six publicly available bulk human lung tissue transcriptomic datasets of COPD patients were intersected with the known mitochondria-related genes from MitoCarta3.0 to obtain mitochondria-related DEGs associated with COPD (MitoDEGs).
Lung ultrasound for assessing disease progression in UIP and NSIP: a comparative study with HRCT and PFT/DLCO.
BMC Pulm Med
January 2025
Tehran Lung Research and Developmental Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Background: This study aims to compare Lung Ultrasound (LUS) findings with High-Resolution Computerized Tomography (HRCT) and Pulmonary Function Tests (PFTs) to detect the severity of lung involvement in patients with Usual Interstitial Pneumonia (UIP) and Non-Specific Interstitial Pneumonia (NSIP).
Methods: A cross-sectional study was conducted on 35 UIP and 30 NSIP patients at a referral hospital. All patients underwent LUS, HRCT, and PFT.
Associations of short-term exposure to air pollution with risk of pulmonary space-occupying lesions morbidity based on a time-series study.
BMC Public Health
January 2025
Department of Thoracic Surgery, the 2nd Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050000, PR China.
Background: Pulmonary space-occupying lesions are typical chronic pulmonary diseases that contribute significantly to healthcare resource use and impose a large disease burden in China. A time-series ecological trend study was conducted to investigate the associations between environmental factors and hospitalizations for pulmonary space-occupying lesions in North of China from 2014 to 2022.
Methods: The DLNM was used to quantify the association of environmental factors with lung cancer admissions.
Lipid metabolism-related genes are involved in the formation of macrophage extracellular traps in allergic airway inflammation.
Genes Immun
January 2025
School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China.
Recent studies have highlighted the critical role of lipid metabolism in macrophages concerning lung inflammation. However, it remains unclear whether lipid metabolism is involved in macrophage extracellular traps (METs). We analyzed the GSE40885 dataset from the GEO database using weighted correlation network analysis (WGCNA) and further selection using the least absolute shrinkage and selection operator (LASSO) regression.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!