TNFalpha-induced macrophage death via caspase-dependent and independent pathways.
TNFalpha-induced macrophage death via caspase-dependent and independent pathways.
复制标题
DOI：
10.1007/s10495-009-0311-4
复制
发表时间：
2009-03
期刊：
影响因子：
7.2
通讯作者：
Pope, Richard M.
中科院分区：
文献类型：
--
作者：
Tran, Tri M.;Temkin, Vladislav;Shi, Bo;Pagliari, Lisa;Daniel, Soizic;Ferran, Christiane;Pope, Richard M.
巨噬细胞是肿瘤坏死因子α的主要来源，但对肿瘤坏死因子α介导的细胞死亡具有高度的抵抗力。以前，我们利用体外分化的人巨噬细胞，我们发现在抑制NF-κB之后，α诱导的Caspase-8的激活有助于DNA片段化，但不是内线粒体膜电位(ΔΨm)丧失或细胞死亡所必需的。我们在此扩展这些观察以证明，当巨噬细胞中的核因子-κB被抑制时，肿瘤坏死因子α改变溶酶体膜通透性。这导致组织蛋白酶B的释放，随后ΔΨm的丢失和Caspase-8独立的细胞死亡。有趣的是，在用κα处理的巨噬细胞中，迅速诱导出具有细胞保护性的、依赖于核因子-肿瘤坏死因子B的蛋白A20。A20在巨噬细胞中的异位表达保留了肿瘤坏死因子α处理后的LMP，从而保护了线粒体的完整性，保护了巨噬细胞免于细胞死亡。这些观察表明，肿瘤坏死因子α在巨噬细胞中触发了caspase8依赖和非依赖的细胞死亡途径，并确定了一种新的机制，通过A20保护这些细胞免受这两种途径的伤害。
Macrophages are the principal source of TNFα, yet they are highly resistant to TNFα-mediated cell death. Previously, employing in vitro differentiated human macrophages, we showed that following the inhibition of NF-κB, TNFα-induced caspase-8 activation contributes to DNA fragmentation but is not necessary for the loss of the inner mitochondrial transmembrane potential (ΔΨm) or cell death. We here extend these observations to demonstrate that, when NF-κB is inhibited in macrophages, TNFα alters lysosomal membrane permeability (LMP). This results in the release of cathepsin B with subsequent loss of ΔΨm and caspase-8 independent cell death. Interestingly, the cytoprotective, NF-κB-dependent protein A20 was rapidly induced in macrophages treated with TNFα. Ectopic expression of A20 in macrophages preserves LMP following treatment with TNFα, and as a result, mitochondrial integrity is safeguarded and macrophages are protected from cell death. These observations demonstrate that TNFα triggers both caspase 8-dependent and -independent cell death pathways in macrophages and identify a novel mechanism by which A20 protects these cells against both pathways.
登录
查看更多内容
影响因子：
4.8
作者：
Bidère, N;Lorenzo, HK;Senik, A
通讯作者：
Senik, A
影响因子：
56.9
作者：
Lee, EG;Boone, DL;Ma, A
通讯作者：
Ma, A
影响因子：
--
作者：
Bai, SC;Liu, HT;Pope, RM
通讯作者：
Pope, RM
影响因子：
64.5
作者：
AdamKlages, S;Adam, D;Kronke, M
通讯作者：
Kronke, M
影响因子：
15.9
作者：
COLLETTI, LM;REMICK, DG;CAMPBELL, DA
通讯作者：
CAMPBELL, DA