Nuclear factor-κB activation and postischemic inflammation are suppressed in CD36-null mice after middle cerebral artery occlusion
Nuclear factor-κB activation and postischemic inflammation are suppressed in CD36-null mice after middle cerebral artery occlusion
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DOI：
10.1523/jneurosci.5205-07.2008
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发表时间：
2008-02-13
影响因子：
5.3
通讯作者：
Iadecola, Costantino
中科院分区：
文献类型：
--
作者：
Kunz, Alexander;Abe, Takato;Iadecola, Costantino
CD 36是一种B类清道夫受体，参与多种功能，包括炎症信号传导，也可能通过尚未确定的机制促进缺血性脑损伤。我们研究了CD 36是否参与了伴随脑缺血的炎症反应的分子事件，并可能导致组织损伤。我们发现，激活核因子-κ B B，一个转录因子，协调缺血后的基因表达，减弱在CD 36基因敲除小鼠大脑中动脉闭塞。抑制中性粒细胞浸润和脑缺血引起的胶质细胞反应。用诱导型一氧化氮合酶抑制剂（一种导致组织损伤的酶）治疗可减少野生型小鼠的缺血性脑损伤，但在CD 36缺失小鼠中则不然。与脑缺血相反，脑室内注射白细胞介素-1 β诱导的分子和细胞炎症变化在CD 36-null小鼠中没有减弱。这些发现揭示了CD 36在导致核因子-κ B活化和缺血后炎症的早期分子事件中的新作用。抑制CD 36信号传导可能是一种有价值的治疗方法，以抵消缺血后炎症的有害影响。
CD36, a class-B scavenger receptor involved in multiple functions, including inflammatory signaling, may also contribute to ischemic brain injury through yet unidentified mechanisms. We investigated whether CD36 participates in the molecular events underlying the inflammatory reaction that accompanies cerebral ischemia and may contribute to the tissue damage. We found that activation of nuclear factor-kappa B, a transcription factor that coordinates postischemic gene expression, is attenuated in CD36-null mice subjected to middle cerebral artery occlusion. The infiltration of neutrophils and the glial reaction induced by cerebral ischemia were suppressed. Treatment with an inhibitor of inducible nitric oxide synthase, an enzyme that contributes to the tissue damage, reduced ischemic brain injury in wild-type mice, but not in CD36 nulls. In contrast to cerebral ischemia, the molecular and cellular inflammatory changes induced by intracerebroventricular injection of interleukin-1 beta were not attenuated in CD36-null mice. The findings unveil a novel role of CD36 in early molecular events leading to nuclear factor-kappa B activation and postischemic inflammation. Inhibition of CD36 signaling may be a valuable therapeutic approach to counteract the deleterious effects of postischemic inflammation.