title: Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) reduces vascular endothelial growth factor expression in allergen-induced airway inflammation.
abstract: Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of bronchial asthma. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) has been implicated in regulating cell survival signaling through the phosphoinositide 3-kinase (PI3K)/Akt pathway. The key role of PI3K in VEGF-mediated signal transduction is established. However, the effects of PTEN on VEGF-mediated signaling in asthma are unknown. This study aimed to determine the effect of PI3K inhibitors and PTEN on VEGF expression in allergen-induced airway inflammation. We have used a female C57BL/6 mouse model for asthma to determine the role of PTEN in allergen-induced airway inflammation, specifically in the expression of VEGF. Allergen-induced airway inflammation leads to increased activity of PI3K in lung tissue. These mice develop the following typical pathophysiological features of asthma in the lungs: increased numbers of inflammatory cells of the airways; airway hyper-responsiveness; increased expression of interleukin (IL)-4, IL-5, IL-13, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, regulated on activation normal T cell expressed and secreted (RANTES), and eotaxin; increased vascular permeability; and increased levels of VEGF. Administration of PI3K inhibitors or adenoviruses carrying PTEN cDNA reduced the symptoms of asthma and decreased the increased levels of plasma extravasation and VEGF in allergen-induced asthmatic lungs. These results indicate that PTEN reduces VEGF expression in allergen-induced airway inflammation.
authors.affiliation: Department of Internal Medicine, Chonbuk National University Medical School, San 2-20, Geumamdong, deokjin-gu, Jeonju, Jeonbuk 561-180, South Korea.
authors.forename: Kyung Sun
authors.initials: KS
authors.lastname: Lee
authors.forename: So Ri
authors.initials: SR
authors.lastname: Kim
authors.forename: Seoung Ju
authors.initials: SJ
authors.lastname: Park
authors.forename: Ho Kyung
authors.initials: HK
authors.lastname: Lee
authors.forename: Hee Sun
authors.initials: HS
authors.lastname: Park
authors.forename: Kyung Hoon
authors.initials: KH
authors.lastname: Min
authors.forename: Sun Mi
authors.initials: SM
authors.lastname: Jin
authors.forename: Yong Chul
authors.initials: YC
authors.lastname: Lee
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000485:Allergens / Q000276:immunology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D002872:Chromosome Deletion; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007375:Interleukin-1 / Q000378:metabolism; D008168:Lung / Q000737:chemistry / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009025:Morpholines / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D051059:PTEN Phosphohydrolase / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D012130:Respiratory Hypersensitivity / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077191:Wortmannin
chemical_list: D000485:Allergens; D000730:Androstadienes; D015815:Cell Adhesion Molecules; D018925:Chemokines; D002867:Chromones; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D010047:Ovalbumin; D040262:Receptors, Vascular Endothelial Growth Factor; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; D000077191:Wortmannin