Division of Hematology, Rheumatology and Respiratory Medicine, Kagawa University, Kagawa, Japan.
J Inflamm Res. 2011;4:127-38. doi: 10.2147/JIR.S19461. Epub 2011 Sep 15.
Inflammation contributes to the development of fibrotic and malignant diseases. We assessed the ability of inflammatory cytokines to modulate endothelial cell survival and functions related to tissue repair/remodeling. Treatment with interleukin (IL)-1β or tumor necrosis factor (TNF)-α (2 ng/mL) led to human pulmonary artery endothelial cells becoming spindle-shaped fibroblast-like cells. However, immunoblot and DNA microarray showed no change in most endothelial and mesenchymal markers. In the presence of IL-1β or TNF-α, cells were resistant to apoptosis induced by deprivation of serum and growth factor, and were more migratory. In addition, cells treated with IL-1β or TNF-α contracted collagen gels more robustly. In contrast, transforming growth factor-β1 did not induce these responses. RNA interference targeting nuclear factor (NF)-κB p65 blocked the effects of IL-1β or TNF-α on cell morphologic change, survival, migration, and collagen gel contraction. These results suggest that endothelial cells may contribute to tissue repair/remodeling via the NF-κB signaling in a milieu of airway inflammation.
炎症会导致纤维性和恶性疾病的发展。我们评估了炎症细胞因子调节内皮细胞存活和与组织修复/重塑相关功能的能力。用白细胞介素 (IL)-1β或肿瘤坏死因子 (TNF)-α（2ng/mL）处理会导致人肺动脉内皮细胞变成梭形成纤维样细胞。然而，免疫印迹和 DNA 微阵列显示大多数内皮和间充质标志物没有变化。在存在 IL-1β或 TNF-α的情况下，细胞对血清和生长因子剥夺诱导的凋亡具有抗性，并且迁移能力更强。此外，用 IL-1β或 TNF-α处理的细胞更有力地收缩胶原凝胶。相比之下，转化生长因子-β1 不会引起这些反应。针对核因子 (NF)-κB p65 的 RNA 干扰阻断了 IL-1β或 TNF-α对细胞形态变化、存活、迁移和胶原凝胶收缩的影响。这些结果表明，内皮细胞可能通过气道炎症环境中的 NF-κB 信号通路促进组织修复/重塑。
