Bcl-2 and Bcl-XL serve an anti-inflammatory function in endothelial tells through inhibition of NF-κB
Bcl-2 and Bcl-XL serve an anti-inflammatory function in endothelial tells through inhibition of NF-κB
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DOI：
10.1172/jci2517
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发表时间：
1999-02-01
影响因子：
15.9
通讯作者：
Ferran, C
中科院分区：
文献类型：
--
作者：
Badrichani, AZ;Stroka, DM;Ferran, C
为了维持血管屏障的完整性，内皮细胞（EC）能够抵抗细胞死亡。这种抗性的分子基础可以通过抗凋亡基因（例如 bcl 家族成员）的功能来解释。 Bcl-2 或 Bcl-X-L 的过度表达可保护 EC 免受肿瘤坏死因子 (TNF) 介导的细胞凋亡。此外，Bcl-2 或 Bcl-X-L 抑制 NF-κ B 的激活，从而抑制促炎基因的上调。 EC 中 Bcl-2 介导的 NF-kappa B 抑制发生在 I kappa B α 降解的上游，而不影响 p65 介导的反式激活。 EC中bcl基因的过度表达不影响其他转录因子。使用 Bcl-2 的缺失突变体，Bcl-2 nas 的 NF-kappa B 抑制功能映射到 bcl 同源结构域 BH2 和 BH4，而所有 BH 结构域都是抗凋亡功能所必需的。这些数据表明，Bcl-2 和 Bcl-X-L 属于细胞保护反应，可以抵消促凋亡和促炎症损伤，并恢复 EC 的生理抗炎表型。通过抑制 NF-kappa B 而不使细胞（与 I kappa B α 一样）对 TNF 介导的细胞凋亡敏感，Bcl-2 和 Bcl-X-L 是在不希望 EC 丢失和不受限制的激活的病理条件下进行 EC 基因工程的主要候选者。
To maintain the integrity of the vascular barrier, endothelial cells (EC) are resistant to cell death. The molecular basis of this resistance may be explained by the function of antiapoptotic genes such as bcl family members. Overexpression of Bcl-2 or Bcl-X-L protects EC from tumor necrosis factor (TNF)-mediated apoptosis. In addition, Bcl-2 or Bcl-X-L inhibits activation of NF-kappa B and thus upregulation of proinflammatory genes. Bcl-2-mediated inhibition of NF-kappa B in EC occurs upstream of I kappa B alpha degradation without affecting p65-mediated transactivation. Overexpression of bcl genes in EC does not affect other transcription factors. Using deletion mutants of Bcl-2, the NF-kappa B inhibitory function of Bcl-2 nas mapped to bcl homology domains BH2 and BH4, whereas all BH domains were required for the antiapoptotic function. These data suggest that Bcl-2 and Bcl-X-L belong to a cytoprotective response that counteracts proapoptotic and proinflammatory insults and restores the physiological anti-inflammatory phenotype to the EC. By inhibiting NF-kappa B without sensitizing the cells (as with I kappa B alpha) to TNF-mediated apoptosis, Bcl-2 and Bcl-X-L are prime candidates for genetic engineering of EC in pathological conditions where EC loss and unfettered activation are undesirable.