Preventive and Therapeutic Effects of Phosphoinositide 3-Kinase Inhibitors on Acute Lung Injury
(2011) In Chest 140(2). p.391-400- Abstract
- Background: Phosphoinositide 3-kinases (PI3Ks) are involved in a number of biologic responses. Recent preclinical studies demonstrated that the PI3K-dominant signal pathway could play an important role in the development of acute lung injury, although the mechanism remains unclear. Methods: CD-1 mice were administered different PI3K inhibitors either intranasally or intragastrically once a day for 3 days before intratracheal instillation of lipopolysaccharide at 4 h and 24 h. Effects of SHBM1009 on lipopolysaccharide-induced capillary permeability, leukocyte distribution and activation, and epithelial cell function were measured. Therapeutic effects of SHBM1009 on pancreatic elastase-induced lung injury were evaluated in rats. Results: The... (More)
- Background: Phosphoinositide 3-kinases (PI3Ks) are involved in a number of biologic responses. Recent preclinical studies demonstrated that the PI3K-dominant signal pathway could play an important role in the development of acute lung injury, although the mechanism remains unclear. Methods: CD-1 mice were administered different PI3K inhibitors either intranasally or intragastrically once a day for 3 days before intratracheal instillation of lipopolysaccharide at 4 h and 24 h. Effects of SHBM1009 on lipopolysaccharide-induced capillary permeability, leukocyte distribution and activation, and epithelial cell function were measured. Therapeutic effects of SHBM1009 on pancreatic elastase-induced lung injury were evaluated in rats. Results: The data demonstrated that the local delivery of PI3K inhibitors played more effective roles in the prevention of endotoxin-induced lung injury than the systemic delivery. The preventive effects of PI3K inhibitors varied most likely because of chemical properties, targeting sites, and pharmacokinetics. The local PI3K inhibitors prevented both endotoxin- and elastase-induced lung injury in mice and rats, possibly through directly inhibiting or inactivating the function of airway epithelial cells, which could not produce chemoattractant factors to activate neutrophils and macrophages. Conclusions: PI3K may be a therapeutic target for lung injury, and local delivery of PI3K inhibitors may be one of the optimal approaches for the therapy. CHEST 2011; 140(2):391-400 (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2162113
- author
- Chen, Chengshui ; Fang, Xiaocong ; Wang, Yaoli ; Li, Yuping ; Wang, Diane ; Zhao, Xia LU ; Bai, Chunxue and Wang, Xiangdong
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Chest
- volume
- 140
- issue
- 2
- pages
- 391 - 400
- publisher
- American College of Chest Physicians
- external identifiers
-
- wos:000293994100023
- scopus:80051526123
- pmid:21636664
- ISSN
- 1931-3543
- DOI
- 10.1378/chest.10-3060
- language
- English
- LU publication?
- yes
- id
- 9c40a4aa-5ab8-43a7-b134-7c0b54843139 (old id 2162113)
- date added to LUP
- 2016-04-01 14:02:48
- date last changed
- 2022-01-27 22:33:32
@article{9c40a4aa-5ab8-43a7-b134-7c0b54843139,
abstract = {{Background: Phosphoinositide 3-kinases (PI3Ks) are involved in a number of biologic responses. Recent preclinical studies demonstrated that the PI3K-dominant signal pathway could play an important role in the development of acute lung injury, although the mechanism remains unclear. Methods: CD-1 mice were administered different PI3K inhibitors either intranasally or intragastrically once a day for 3 days before intratracheal instillation of lipopolysaccharide at 4 h and 24 h. Effects of SHBM1009 on lipopolysaccharide-induced capillary permeability, leukocyte distribution and activation, and epithelial cell function were measured. Therapeutic effects of SHBM1009 on pancreatic elastase-induced lung injury were evaluated in rats. Results: The data demonstrated that the local delivery of PI3K inhibitors played more effective roles in the prevention of endotoxin-induced lung injury than the systemic delivery. The preventive effects of PI3K inhibitors varied most likely because of chemical properties, targeting sites, and pharmacokinetics. The local PI3K inhibitors prevented both endotoxin- and elastase-induced lung injury in mice and rats, possibly through directly inhibiting or inactivating the function of airway epithelial cells, which could not produce chemoattractant factors to activate neutrophils and macrophages. Conclusions: PI3K may be a therapeutic target for lung injury, and local delivery of PI3K inhibitors may be one of the optimal approaches for the therapy. CHEST 2011; 140(2):391-400}},
author = {{Chen, Chengshui and Fang, Xiaocong and Wang, Yaoli and Li, Yuping and Wang, Diane and Zhao, Xia and Bai, Chunxue and Wang, Xiangdong}},
issn = {{1931-3543}},
language = {{eng}},
number = {{2}},
pages = {{391--400}},
publisher = {{American College of Chest Physicians}},
series = {{Chest}},
title = {{Preventive and Therapeutic Effects of Phosphoinositide 3-Kinase Inhibitors on Acute Lung Injury}},
url = {{http://dx.doi.org/10.1378/chest.10-3060}},
doi = {{10.1378/chest.10-3060}},
volume = {{140}},
year = {{2011}},
}