Department of Pathology, VUmc University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands,
Cell Biochem Biophys. 2013 Nov;67(2):247-54. doi: 10.1007/s12013-013-9773-7.
Angiogenesis and microvascular leakage are features of chronic inflammatory diseases of which molecular mechanisms are poorly understood. We investigated the effects of interleukin-1β (IL-1β) on the expression and secretion of vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) in porcine airway smooth muscle cells (PASMC) in relation to a nitric oxide (NO) pathway. Serum-deprived (48 h) PASMC were stimulated with IL-1β alone or with NO donor, L-arginine and/or NO synthase inhibitor L-NAME for 4 and 24 h. IL-1β did not affect PlGF release, but augmented VEGF release (2.4-fold) after 24 h. VEGF release was inhibited by L-NAME (531.8 ± 52 pg/ml), but restored and further elevated by L-arginine (1,529 ± 287 pg/ml). IL-1β up-regulated VEGF mRNA (1.8-fold) and this response was attenuated by L-NAME (1.1-fold) and augmented by L-arginine (3.8-fold) at 4 h. Restoration of a NO pathway by L-arginine in L-NAME-treated cells resulted in elevated VEGF mRNA levels (2.2-fold). [(3)H]Thymidine incorporation assay revealed enhanced porcine pulmonary artery endothelial cell proliferation in response to IL-1β, VEGF and PlGF, and this mitogenic effect was not influenced via the NO pathway. Our results suggest that a NO pathway modulates VEGF synthesis during inflammation contributing to bronchial angiogenesis and vascular leakage.
血管生成和微血管渗漏是慢性炎症性疾病的特征，其分子机制尚不清楚。我们研究了白细胞介素 1β（IL-1β）对猪气道平滑肌细胞（PASMC）中血管内皮生长因子（VEGF）和胎盘生长因子（PlGF）表达和分泌的影响，以及一氧化氮（NO）途径。用 IL-1β单独或用 NO 供体 L-精氨酸和/或 NO 合酶抑制剂 L-NAME 刺激血清剥夺（48 h）的 PASMC 4 和 24 h。IL-1β 不影响 PlGF 的释放，但在 24 h 后增加 VEGF 的释放（2.4 倍）。L-NAME（531.8±52 pg/ml）抑制 VEGF 释放，但 L-精氨酸（1,529±287 pg/ml）恢复并进一步升高。IL-1β 上调 VEGF mRNA（1.8 倍），这种反应被 L-NAME 减弱（1.1 倍），L-精氨酸增强（3.8 倍）在 4 h。用 L-精氨酸恢复 NO 途径会导致 L-NAME 处理的细胞中 VEGF mRNA 水平升高（2.2 倍）。[（3）H]胸苷掺入试验显示，猪肺动脉内皮细胞对 IL-1β、VEGF 和 PlGF 的增殖反应增强，而这种促有丝分裂作用不受 NO 途径的影响。我们的结果表明，NO 途径在炎症过程中调节 VEGF 的合成，有助于支气管血管生成和血管渗漏。
