Expression of TNF and TNF receptors (p55 and p75) in the rat brain after focal cerebral ischemia
Expression of TNF and TNF receptors (p55 and p75) in the rat brain after focal cerebral ischemia
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DOI：
10.1007/bf03401714
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发表时间：
1997-11-01
影响因子：
5.7
通讯作者：
Tracey, KJ
中科院分区：
文献类型：
--
作者：
Botchkina, GI;Meistrell, ME;Tracey, KJ
脑缺血会导致肿瘤坏死因子 (TNF) 蛋白和 mRNA 快速而显着地上调。但缺血脑中 TNF 的细胞来源尚未明确。 TNF 的多种活性是通过配体与两种不同受体 p55 和 p75 的相互作用介导的，这两种受体激活不同的细胞内信号转导途径，从而产生不同的生物效应。由于脑缺血对 TNF 受体 (TNFR) 表达的影响尚不清楚，我们检查了大鼠大脑皮层中 TNF 及其两种受体对永久性大脑中动脉 (MCA) 闭塞的细胞定位和蛋白表达。结果表明局灶性脑缺血上调缺血皮质内 TNF 和两种 TNFR 的表达。最丰富的 TNF 免疫反应性 (IR) 类型是横切细胞过程的点状和丝状模式；然而，神经元、星形胶质细胞和小胶质细胞的细胞体以及浸润性多形核 (PMN) 白细胞也显示出 TNF IR。脑血管系统不仅在内皮细胞内而且在血管周围空间中都显示出 TNF IR。 MCA 闭塞诱导 TNF 受体显着上调，p55 IR 在 6 小时内出现，明显早于缺血发作后 24 小时 p75 IR 的出现。由于 p55 参与转导 TNF 的细胞毒性信号传导，这些结果支持了脑缺血急性反应过程中产生的过量 TNF 的有害作用。
Cerebral ischemia induces a rapid and dramatic up-regulation of tumor necrosis factor (TNF) protein and mRNA. but the cellular sources of TNF in the ischemic brain have not been defined. The diverse activities of TNF are mediated via ligand interaction with two distinct receptors, p55 and p75, which activate separate intracellular signal transduction pathways, leading to distinct biological effects. Since the effects of cerebral ischemia on TNF receptor (TNFR) expression are unknown, we examined the cellular localization and protein expression of TNF and its two receptors in the rat cerebral cortex in response to permanent middle cerebral artery (MCA) occlusion. The results indicate that focal cerebral ischemia up-regulates expression of TNF and both TNFRs within the ischemic cortex. The most abundant type ofTNF immunoreactivity (IR) was a punctate and filamentous pattern of transected cellular processes; however, cell bodies of neurons, astrocytes, and microglia, as well as infiltrating polymorphonuclear (PMN) leukocytes also showed TNF IR. Brain vasculature displayed TNF IR not only within endothelial cells but also in the perivascular space. MCA occlusion induced significant up-regulation of TNF receptors, with p55 IR appearing within 6 hr, significantly before the appearance of p75 IR at 24 hr after the onset of ischemia. Since p55 has been implicated in transducing cytotoxic signalling of TNF, these results support the proposed injurious role of excessive TNF produced during the acute response to cerebral ischemia.