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PI3Kγ activation is required for LPS-induced reactive oxygen species generation in respiratory epithelial cells.
MedLine Citation:
PMID:  22825625     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVE: In this study, we investigated the molecular basis of reactive oxygen species (ROS) generation induced by lipopolysaccharide (LPS) in A549 cells-an alveolar epithelial cell line. EXPERIMENTAL DESIGN: A549 cells or normal human bronchial epithelial (NHBE) cells were stimulated with LPS. ROS generation was measured in A549 cells or NHBE cells pre-treated with a selective inhibitor of phosphatidylinositol 3-kinase γ (PI3Kγ), AS 605240, PI3Kγ siRNA, or a ROS scavenger, pyridoxamine (PM). RESULTS: Treatment of A549 cells or NHBE cells with LPS caused a significant increase in intracellular ROS generation. Pretreatment with the PI3Kγ inhibitor, AS 605240 decreased the LPS-induced increase of ROS generation, phosphorylation of Akt, and production of phosphatidyl 3,4,5-trisphosphate in A549 cells. In addition, interference with siRNA for PI3Kγ significantly reduced LPS-induced ROS generation in A549 cells. Treatment of A549 cells with LPS or hydrogen peroxide increased the nuclear factor-κB (NF-κB) in the nucleus, accompanying an increase in phosphorylation of inhibitory κB-α, degradation of the protein, and reduction of cytosolic NF-κB. Pretreatment with AS 605240 reduced these LPS-induced changes. In addition, pretreatment with PM or N-acetyl cysteine resulted in inhibition of nuclear NF-κB activation. CONCLUSION: These results suggest that PI3Kγ plays a key role in LPS-induced ROS generation in alveolar epithelial cells, thereby activating NF-κB.
Authors:
Hee Jung Kim; So Ri Kim; Jin Kyeong Park; Dong Im Kim; Jae Seok Jeong; Yong Chul Lee
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-24
Journal Detail:
Title:  Inflammation research : official journal of the European Histamine Research Society ... [et al.]     Volume:  -     ISSN:  1420-908X     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9508160     Medline TA:  Inflamm Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Internal Medicine, Research Center for Pulmonary Disorders, Chonbuk National University Medical School, San 2-20 Geumam-dong, Deokjin-gu, Jeonbuk, Jeonju, 561-180, South Korea.
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