Microglial activation state exerts a biphasic influence on brain endothelial cell proliferation by regulating the balance of TNF and TGF-β1.
Microglial activation state exerts a biphasic influence on brain endothelial cell proliferation by regulating the balance of TNF and TGF-β1.
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DOI：
10.1186/1742-2094-7-89
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发表时间：
2010-12-06
影响因子：
9.3
通讯作者：
Milner R
中科院分区：
文献类型：
--
作者：
Welser JV;Li L;Milner R
对脑缺血和其他神经炎症状态的研究表明，新血管形成与小胶质细胞的募集和激活之间存在密切联系，这提高了小胶质细胞可能参与促进血管生成的可能性。由于内皮细胞增殖是血管生成的基本早期步骤，本研究的目的是通过检查小胶质细胞分泌因子对脑内皮细胞（BEC）增殖的影响，使用BrdU掺入来验证这一假设。本研究采用小鼠BEC、小胶质细胞和星形胶质细胞的原代培养。BrdU掺入法检测BEC增殖情况。ELISA用于定量细胞培养上清液中的TNF和TGF-β1水平。小胶质细胞以双相方式调节BEC增殖，来自静息小胶质细胞的小胶质细胞条件培养基（MG-CM）抑制BEC增殖，而来自活化小胶质细胞的MG-CM促进BEC增殖。TGF-β1抑制BEC增殖，TNF促进BEC增殖。ELISA结果显示，TNF和TGF-β1均存在于MG-CM中，而TGF-β1在静息状态的MG-CM中占主导地位，而在活化状态的MG-CM中TNF水平显著升高，使平衡向有利于TNF的方向移动。抗体阻断研究表明，MG-CM抑制或促进BEC增殖的影响主要分别归因于细胞因子TGF-β1和TNF。这些数据表明，小胶质细胞活化状态可能是脑血管生成的重要决定因素;在正常中枢神经系统（CNS）中抑制BEC增殖和新生血管形成，但在神经炎症条件下刺激新毛细血管的生长。
Studies of cerebral ischemia and other neuroinflammatory states have demonstrated a strong association between new vessel formation and microglial recruitment and activation, raising the possibility that microglia may be involved in promoting angiogenesis. As endothelial cell proliferation is a fundamental early step in angiogenesis, the aim of this study was to test this hypothesis by examining the influence of microglial secreted factors on brain endothelial cell (BEC) proliferation using BrdU incorporation. Primary cultures of mouse BEC, microglia and astrocytes were used in this study. Proliferation of BEC was examined by BrdU incorporation. ELISA was used to quantify TNF and TGF-β1 levels within cell culture supernatants. Microglia regulated BEC proliferation in a biphasic manner; microglia conditioned medium (MG-CM) from resting microglia inhibited, while that from activated microglia promoted BEC proliferation. A screen of microglial cytokines revealed that BEC proliferation was inhibited by TGF-β1, but promoted by TNF. ELISA showed that TNF and TGF-β1 were both present in MG-CM, and that while TGF-β1 dominated in resting MG-CM, TNF levels were massively increased in activated MG-CM, shifting the balance in favor of TNF. Antibody-blocking studies revealed that the influence of MG-CM to inhibit or promote BEC proliferation was largely attributable to the cytokines TGF-β1 and TNF, respectively. This data suggests that microglial activation state might be an important determinant of cerebral angiogenesis; inhibiting BEC proliferation and neovascularization in the normal central nervous system (CNS), but stimulating the growth of new capillaries under neuroinflammatory conditions.
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影响因子：
3.3
作者：
Kuo, NT;Benhayon, D;LaManna, JC
通讯作者：
LaManna, JC
影响因子：
9.8
作者：
Astrof S;Hynes RO
通讯作者：
Hynes RO
影响因子：
8.3
作者：
KRUPINSKI, J;KALUZA, J;WANG, JM
通讯作者：
WANG, JM
DOI：
10.1097/00004647-200110000-00011
发表时间：
2001-10-01
影响因子：
6.3
作者：
Manoonkitiwongsa, PS;Jackson-Friedman, C;Lyden, PD
通讯作者：
Lyden, PD
影响因子：
8.3
作者：
CHEN, HH;CHIEN, CH;LIU, HM
通讯作者：
LIU, HM