Decreased Bax expression by mucosal T cells favours resistance to apoptosis in Crohn's disease
Decreased Bax expression by mucosal T cells favours resistance to apoptosis in Crohn's disease
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DOI：
10.1136/gut.49.1.35
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发表时间：
2001-07-01
期刊：
影响因子：
24.5
通讯作者：
Fiocchi, C
中科院分区：
文献类型：
--
作者：
Itoh, J;de la Motte, C;Fiocchi, C
背景-活化的T细胞比静止的T细胞更容易发生凋亡。由于肠T细胞通常表现出较高的活化状态，因此增加的细胞凋亡对于维持粘膜的专门微环境中的免疫稳态可能是必要的。另一方面，在克罗恩病（CD）粘膜T细胞抗凋亡，这表明异常调节细胞死亡mechanism.Aims-To调查的抗和促凋亡Bcl-2家族蛋白的表达差异，细胞凋亡的关键调节因子，循环和粘膜T细胞之间，和可能的改变CD。患者和方法：从10名对照、7名CD和8名溃疡性结肠炎（UC）患者中分离固有层T细胞（LPT），并从健康志愿者中分离外周血T细胞（PBT）。结果：与PET相比，LPT中Bcl-2和Bax的表达水平显著升高，Bcl-x（L）/Bax比值显著降低。在PET中，Bax表达与Bcl-2和Bcl-x（L）高度且显著相关，但在LPT中不存在与Bcl-2的相关性。Bcl-x（L）Bax的显着相关性被保存在CD，但不是UC，LPT. Conclusion-Regulation Bcl-2家族蛋白的表达不同之间的循环和粘膜T细胞，可能潜在的不同的生存潜力。在CD LPT中，低Bax表达和高Bcl-x（L）/Bax比值有利于抗凋亡，并可能导致炎症的慢性化。
Background-Activated T cells are more susceptible to apoptosis than resting T cells. As intestinal T cells normally exhibit a higher state of activation, increased apoptosis may be necessary to maintain immune homeostasis in the specialised microenvironment of the mucosa. On the other hand, in Crohn's disease (CD) mucosal T cells are resistant to apoptosis, suggesting abnormal regulation of cell death mechanisms.Aims-To investigate differences in expression of anti- and proapoptotic Bcl-2 family proteins, key regulators of apoptosis, between circulating and mucosal T cells, and possible alterations in CD. Patients and methods-Lamina propria T cells (LPT) were isolated from 10 control, seven CD, and eight ulcerative colitis (UC) patients, and peripheral blood T cells (PBT) from healthy volunteers. Purified T cells were stained intracellularly for Bcl-2, Bcl-x(L), and Bax, and mean fluorescence intensity measured by flow cytometry.Results-Compared with PET, the expression level of Bcl-2 and Bax, but not Bcl-x(L), was significantly greater in LPT, resulting in lower Bcl-x(L)/Bax ratios. In PET, Bax expression was highly and significantly correlated with both Bcl-2 and Bcl-x(L), but correlation with Bcl-2 was absent in LPT Bax expression in CD, but not UC, LPT was significantly lower than in control LPT, resulting in a significantly higher Bcl-x(L)/Bax ratio. The significant correlation of Bcl-x(L) to Bax was preserved in CD, but not UC, LPT.Conclusions-Regulation of Bcl-2 family protein expression differs between circulating and mucosal T cells, probably underlying diverse survival potentials. In CD LPT, a low Bax expression and a high Bcl-x(L)/Bax ratio favour resistance to apoptosis and may contribute to the chronicity of inflammation.