Vascular endothelial growth factor (VEGF) induces remodeling and enhances TH2-mediated sensitization and inflammation in the lung

Chun Geun Lee, Holger Link, Peter Baluk, Robert J. Homer, Svetlana Chapoval, Vineet Bhandari, Min Jong Kang, Lauren Cohn, Yoon Keun Kim, Donald M. McDonald, Jack A. Elias

Research output: Contribution to journalArticle

442 Scopus citations

Abstract

Exaggerated levels of VEGF (vascular endothelial growth factor) are present in persons with asthma, but the role(s) of VEGF in normal and asthmatic lungs has not been defined. We generated lung-targeted VEGF165 transgenic mice and evaluated the role of VEGF in T-helper type 2 cell (T H2)-mediated inflammation. In these mice, VEGF induced, through IL-13-dependent and -independent pathways, an asthma-like phenotype with inflammation, parenchymal and vascular remodeling, edema, mucus metaplasia, myocyte hyperplasia and airway hyper-responsiveness. VEGF also enhanced respiratory antigen sensitization and TH2 inflammation and increased the number of activated DC2 dendritic cells. In antigen-induced inflammation, VEGF was produced by epithelial cells and preferentially by TH2 versus TH1 cells. In this setting, it had a critical role in T H2 inflammation, cytokine production and physiologic dysregulation. Thus, VEGF is a mediator of vascular and extravascular remodeling and inflammation that enhances antigen sensitization and is crucial in adaptive TH2 inflammation. VEGF regulation may be therapeutic in asthma and other TH2 disorders.

Original languageEnglish (US)
Pages (from-to)1095-1103
Number of pages9
JournalNature medicine
Volume10
Issue number10
DOIs
StatePublished - Oct 1 2004

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Lee, C. G., Link, H., Baluk, P., Homer, R. J., Chapoval, S., Bhandari, V., Kang, M. J., Cohn, L., Kim, Y. K., McDonald, D. M., & Elias, J. A. (2004). Vascular endothelial growth factor (VEGF) induces remodeling and enhances TH2-mediated sensitization and inflammation in the lung. Nature medicine, 10(10), 1095-1103. https://doi.org/10.1038/nm1105