血管生成
基质凝胶
炎症
趋化因子
新生血管
血管内皮生长因子
促炎细胞因子
细胞生物学
骨髓
内皮干细胞
免疫学
生物
细胞因子
癌症研究
体外
生物化学
血管内皮生长因子受体
作者
Yaron Carmi,Elena Voronov,Shahar Dotan,Nitza Lahat,Michal A. Rahat,Mina Fogel,Monika Huszar,Malka R. White,Charles A. Dinarello,Ron N. Apte
出处
期刊:Journal of Immunology
[American Association of Immunologists]
日期:2009-09-15
卷期号:183 (7): 4705-4714
被引量:215
标识
DOI:10.4049/jimmunol.0901511
摘要
Abstract Inflammation and angiogenesis are pivotal processes in the progression of many diseases, including malignancies. A hypoxic microenvironment often results in a milieu of proinflammatory and proangiogenic cytokines produced by infiltrating cells. We assessed the role of macrophage-derived hypoxia-associated cytokines in promoting inflammation and angiogenesis. Supernatants of macrophages, stimulated under hypoxia with or without an inflammatory stimulus (LPS), promoted angiogenesis when incorporated into Matrigel plugs. However, neutralization of IL-1 in the supernatants, particularly IL-1β, completely abrogated cell infiltration and angiogenesis in Matrigel plugs and reduced vascular endothelial growth factor (VEGF) levels by 85%. Similarly, supernatants from macrophages of IL-1β knockout mice did not induce inflammatory or angiogenic responses. The importance of IL-1 signaling in the host was demonstrated by the dramatic reduction of inflammatory and angiogenic responses in Matrigel plugs that contained macrophage supernatants from control mice which had been implanted in IL-1 receptor type I knockout mice. Myeloid cells infiltrating into Matrigel plugs were of bone marrow origin and represented the major source of IL-1 and other cytokines/chemokines in the plugs. Cells of endothelial lineage were the main source of VEGF and were recruited mainly from neighboring tissues, rather than from the bone marrow. Using the aortic ring sprouting assay, it was shown that in this experimental system, IL-1 does not directly activate endothelial cell migration, proliferation and organization into blood vessel-like structures, but rather activates infiltrating cells to produce endothelial cell activating factors, such as VEGF. Thus, targeting IL-1β has the potential to inhibit angiogenesis in pathological situations and may be of considerable clinical value.
科研通智能强力驱动
Strongly Powered by AbleSci AI