Corticotropin-releasing factor (CRF) can directly affect brain microvessel endothelial cells.
Corticotropin-releasing factor (CRF) can directly affect brain microvessel endothelial cells.
复制标题
促肾上腺皮质激素释放因子（CRF）可直接影响脑微血管内皮细胞。
DOI：
10.1016/s0006-8993(03)02237-6
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发表时间：
2003
期刊：
影响因子：
2.9
通讯作者：
Theoharides,TheoharisC
中科院分区：
文献类型：
--
作者：
Esposito,Pamela;Basu,Subimal;Letourneau,Richard;Jacobson,Stanley;Theoharides,TheoharisC
应激通过释放促肾上腺皮质激素释放因子(CRF)激活下丘脑-垂体-肾上腺(HPA)轴，导致糖皮质激素的产生，从而下调免疫反应。然而，通过CRF的急性应激也有促炎作用。我们之前的研究表明，急性应激增加大鼠血脑屏障(BBB)的通透性，这一影响涉及脑肥大细胞和CRF，因为在W/Wvmast细胞缺陷小鼠中没有这种作用，并被CRF受体拮抗剂Antalarmin阻断。我们研究了CRF对分离自大鼠和牛脑的脑微血管内皮细胞(BMEC)是否也有直接作用。培养BMEC，并用电子显微镜进行鉴定。培养的BMEC经Western印迹分析鉴定出CRF受体蛋白；CRF或其结构类似物尿皮质素(UCN)的刺激表明，该受体在功能上与腺苷环化酶偶联，使环磷酸腺苷(CAMP)水平增加2倍。这些发现表明，CRF可能会影响BMEC的结构或功能，正如其他研究报告的cAMP水平升高一样。因此，CRF可能除了通过脑肥大细胞介导的任何作用外，还可能直接调节血脑屏障通透性。
Stress activates the hypothalamic–pituitary–adrenal (HPA) axis through release of corticotropin releasing factor (CRF), leading to production of glucocorticoids that down regulate immune responses. However, acute stress via CRF also has pro-inflammatory effects. We previously showed that acute stress increases rat blood–brain barrier (BBB) permeability, an effect involving brain mast cells and CRF, as it was absent in W/Wvmast cell-deficient mice and was blocked by the CRF-receptor antagonist, Antalarmin. We investigated if CRF could also have a direct action on brain microvessel endothelial cells (BMEC) isolated from rat and bovine brain. BMEC were cultured and identified by electron microscopy. Western blot analysis of cultured BMEC identified CRF receptor protein; stimulation with CRF, or it structural analogue urocortin (Ucn) showed that the receptor is functionally coupled to adenylate cyclase as it increased cyclic AMP (cAMP) levels by 2-fold. These findings suggest that CRF could affect BMEC structure or function, as reported for increased cAMP levels by other studies. It is, therefore, possible that CRF may directly regulate BBB permeability, in addition to any effect mediated via brain mast cells.