Expression and regulation of vascular endothelial growth factor in human pulmonary epithelial cells

Vascular endothelial growth factor (VEGF) is a potent endothelial cell grow th and permeability factor highly expressed in rodent alveolar epithelium a fter injury and repair. To investigate VEGF synthesis in human lung epithel ial cells, we examined VEGF expression by cultured cells under basal condit ions and after cytokine treatment or oxidative stress. Basal VEGF expressio n was detected in transformed human epithelial cell lines (A549 and 1HAEo(- )) and in primary human bronchial epithelial cells with RT-PCR, Western blo t, and immunocytochemistry. Among the cytokines tested, only transforming g rowth factor-beta 1 increased the levels of excreted VEGF(165) as measured by ELISA. Under hypoxia (0% O-2 for 24 h), the VEGF(165) level increased fi vefold, and this effect was O-2 concentration dependent. VEGF concentration s in the medium of all the cell types studied reached values similar to tho se found in bronchoalveolar lavage fluids from normal patients. Endothelial cells (human umbilical vein endothelial cells) exposed to conditioned medi um from primary bronchial epithelial cell cultures showed an increased grow th rate, which was inhibited in the presence of a specific neutralizing ant ibody to VEGF. These results suggest that lung epithelial cells participate in the endothelial repair and angiogenesis that follow lung injury through the synthesis of VEGF.