Vascular endothelial growth factor (VEGF) induces remodeling and enhances T_H2-mediated sensitization and inflammation in the lung

Nature Medicine 10:1095 - 1103 (2004)

Speaker:王瑋祥                              Time : 14:00-15:00, Dec. 29, 2004

Commentator :王志堯 老師                                 Place : Room 601

Abstract :

  Exaggerated T_H2 inflammation and airway remodeling are cornerstones in the pathogenesis of asthma.  Exaggerated levels of VEGF have been detected in patients with asthma and correlate directly with disease activity. However, the role of VEGF in the pathogenesis in the lung has not been defined. In this study, the authors first generated lung-specific-doxycycline-on VEGF transgenic mice. They found that VEGF is a potent inducer of angiogenesis and edema in the airway and lung of the transgenic mice. They also proved that VEGF an asthma-like phenotype inhistology and physiologyin the mice. The asthma-like phenomenon included two standard responses. Airway inflammation increased macrophages, lymphocytes and eosinophils in bronchoalveolar lavage (BAL). The other is airway remodeling, including IL-13-independent subepithelial fibrosis, smooth muscle hyperplasia and IL-13-dependent mucus metaplasia, and airway hyper-responsiveness (AHR).¹ Second, impressive levels of sensitization are caused by even exposure to a low-level antigen in transgenic mice. This is evidence to demonstrate that VEGF augments respiratory T_H2 sensitization, which includes antigen-induced spleen cell proliferation, antigen-specific IgG₁ production, and increase of activated pulmonary DC2 dendrtic cells. Finally, they showed that the effect of VEGF could be decreased by SU1498, a VEGF inhibitor, in sensitized and challenged wild-type mice. Taking together, VEGF is a mediator of vascular, extravascular remodeling and inflammation. VEGF also enhances antigen sensitization and is crucial in adaptive T_H2 inflammation.² Regulation of VEGF may have therapeutic potential in asthma and other T_H2 disorders.

References :

1.     Lee CG, et al. Transgenic overexpression of interleukin (IL)-10 in the lung causes mucus metaplasia, tissue inflammation, and airway remodeling via IL-13-dependent and -independent pathways. J Biol Chem. 2002 ; 277:35466-74.

2.     Rothenberg ME. VEGF obstructs the lungs. Nat Med. 2004 Oct; 10(10):1041-2.

3.     Lee CG, et al. Vascular endothelial growth factor (VEGF) induces remodeling and enhances T_H2-mediated sensitization and inflammation in the lung. Nat Med. 2004; 10:1095-103.