The activity of soluble VCAM-1 in angiogenesis stimulated by IL-4 and IL-13
The activity of soluble VCAM-1 in angiogenesis stimulated by IL-4 and IL-13
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DOI：
10.4049/jimmunol.165.5.2818
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发表时间：
2000-09-01
影响因子：
4.4
通讯作者：
Kuwano, W
中科院分区：
文献类型：
--
作者：
Fukushi, J;Ono, M;Kuwano, W
IL-13是一种多功能淋巴因子，与IL-4具有许多生物学特性。我们先前观察到IL-4在体外和体内显示血管生成活性。在这项研究中，我们研究了IL-13在体外和体内对血管生成的影响，以及潜在的机制。人IL-13显著刺激人微血管内皮细胞和牛主动脉内皮细胞在胶原凝胶中形成管状结构，其刺激程度是不存在细胞因子的对照组的约3倍。当植入大鼠角膜时，鼠IL-13的给药导致新血管形成。与IL-4 R共施用中和mAb抑制体外肾小管形态发生和由IL-4或IL-13诱导的STAT 6活化。IL-4和IL-13均显著增加血管内皮细胞中VCAM-1的mRNA水平，并且响应于IL-4或IL-13也刺激可溶性形式的VCAM-1的产生。在体外给予抗VCAM-1抗体阻断了IL-4和IL-13诱导的肾小管形态发生。抗大鼠cu、整联蛋白亚基的抗体也能抑制IL-4和IL-13在体内诱导的大鼠角膜血管生成。这些发现表明，依赖于IL-4和IL-13的血管生成主要通过可溶性VCAM-1/α（4）整联蛋白途径介导。
IL-13 is a multifunctional lymphokine sharing a number of biological properties with IL-4. We previously observed that IL-4 shows angiogenic activities in vitro as well as in vivo. In this study we examined the effect of IL-13 on angiogenesis in vitro and in vivo and also the underlying mechanisms. Human IL-13 significantly stimulated the formation of tube-like structures in collagen gels by human microvascular endothelial cells and bovine aortic endothelial cells by about 3-fold over the controls in the absence of the cytokines. Administration of murine IL-13 led to neovascularization when implanted in the rat cornea. Coadministration of neutralizing mAb to the IL-4R inhibited both tubular morphogenesis in vitro and activation of STAT6 induced by IL-4 or IL-13. Both IL-4 and IL-13 markedly increased mRNA levels of VCAM-1 in vascular endothelial cells, and the production of the soluble form of VCAM-1 was also stimulated in response to IL-4 or IL-13. Administration of anti-VCAM-1 Ab in vitro blocked tubular morphogenesis induced by IL-4 and IL-13. Angiogenesis induced in vivo in rat cornea by IL-4 and IL-13 was also inhibited by Ab against the rat cu, integrin subunit. These findings suggest that angiogenesis dependent on IL-4 and IL-13 is mainly mediated through a soluble VCAM-1/alpha (4) integrin pathway.