Interleukin-1α expression precedes IL-1β after ischemic brain injury and is localised to areas of focal neuronal loss and penumbral tissues.

Interleukin-1α expression precedes IL-1β after ischemic brain injury and is localised to areas of focal neuronal loss and penumbral tissues.
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白介素1α的表达在缺血性脑损伤后先于IL-1β,并定位于局灶性神经元丧失和半月组织。

DOI:
10.1186/1742-2094-8-186
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发表时间:
2011-12-29
影响因子:
9.3
通讯作者:
Denes A
Denes A
中科院分区:
医学1区
文献类型:
--
作者:
Luheshi NM;Kovács KJ;Lopez-Castejon G;Brough D;Denes A

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脑缺血是一种破坏性疾病,其结果受到炎症过程的严重影响,炎症过程可加重由血液供应减少引起的原发性损伤。细胞因子白细胞介素-1 α(IL-1α)和IL-1β是缺血性脑损伤的关键因素。然而,很少有证据表明IL-1表达在蛋白水平上发生足够早(数小时内),以影响中风后的脑损伤。为了确定这一点,我们研究了脑缺血后IL-1α和IL-1β表达的时间和空间分布。我们在此报道,在小鼠中,早在大脑中动脉闭塞诱导的缺血再灌注后4小时,IL-1α而不是IL-1β在缺血半球的小胶质细胞样细胞中表达,这与IL-1α mRNA的上调平行。缺血24 h后IL-1α表达与局灶性血脑屏障破坏和神经元死亡密切相关,主要在梗死周围的半暗带附近。IL-1α在损伤区的亚细胞分布不均匀,表明其受到调节。IL-1α在局灶性神经元损伤区的早期表达表明,它是IL-1参与脑缺血后早期炎症反应的主要形式。这增加了越来越多的证据表明IL-1α是无菌炎症反应的关键介质。
Cerebral ischemia is a devastating condition in which the outcome is heavily influenced by inflammatory processes, which can augment primary injury caused by reduced blood supply. The cytokines interleukin-1α (IL-1α) and IL-1β are key contributors to ischemic brain injury. However, there is very little evidence that IL-1 expression occurs at the protein level early enough (within hours) to influence brain damage after stroke. In order to determine this we investigated the temporal and spatial profiles of IL-1α and IL-1β expression after cerebral ischemia. We report here that in mice, as early as 4 h after reperfusion following ischemia induced by occlusion of the middle cerebral artery, IL-1α, but not IL-1β, is expressed by microglia-like cells in the ischemic hemisphere, which parallels an upregulation of IL-1α mRNA. 24 h after ischemia IL-1α expression is closely associated with areas of focal blood brain barrier breakdown and neuronal death, mostly near the penumbra surrounding the infarct. The sub-cellular distribution of IL-1α in injured areas is not uniform suggesting that it is regulated. The early expression of IL-1α in areas of focal neuronal injury suggests that it is the major form of IL-1 contributing to inflammation early after cerebral ischemia. This adds to the growing body of evidence that IL-1α is a key mediator of the sterile inflammatory response.
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