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 P. Chapoval,Vineet Bhandari,Min-Jong Kang,Lauren Cohn,Yoon Keun Kim,Donald M. McDonald,Jack A. Elias +10 more
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TLDR
VEGF is a mediator of vascular and extravascular remodeling and inflammation that enhances antigen sensitization and is crucial in adaptive TH2 inflammation and VEGF regulation may be therapeutic in asthma and other TH2 disorders.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 (TH2)-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 TH2 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.read more
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References
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Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production
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Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo
TL;DR: Findings implicate the angiogenesis factor VEGF in neurogenesis as well in murine cerebral cortical cultures and in adult rat brain in vivo.
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Gavin Thurston,John S. Rudge,Ella Ioffe,Hao Zhou,Leorah Ross,Susan D. Croll,Nicole Glazer,Jocelyn Holash,Donald M. McDonald,George D. Yancopoulos +9 more
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Stephanie C. Eisenbarth,Damani A. Piggott,James W. Huleatt,Irene Visintin,Christina A. Herrick,Kim Bottomly +5 more
TL;DR: It is reported that low level inhaled LPS signaling through TLR4 is necessary to induce Th2 responses to inhaled antigens in a mouse model of allergic sensitization and provides a potential mechanistic explanation of epidemiological data on endotoxin exposure and asthma prevalence.
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Respiratory Syncytial Virus Bronchiolitis in Infancy Is an Important Risk Factor for Asthma and Allergy at Age 7
TL;DR: RSV bronchiolitis in infancy severe enough to cause hospitalization was highly associatied with the development of asthma and allergic sensitization up to age 7(1)/ (2).