Differential regulation of type I and type II interleukin-1 receptors in focal brain inflammation
Differential regulation of type I and type II interleukin-1 receptors in focal brain inflammation
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DOI：
10.1111/j.1460-9568.2005.03965.x
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发表时间：
2005-03-01
影响因子：
3.4
通讯作者：
Anthony, DC
中科院分区：
文献类型：
--
作者：
Docagne, F;Campbell, SJ;Anthony, DC
脑的大多数病理具有炎症组分，与从驻留和浸润细胞释放细胞因子如白细胞介素-1 β（IL-1 β）相关。IL-1 I型受体（IL-1 RI）启动信号级联，但II型受体（IL-1 RII）作为诱饵受体。在这里，我们研究了IL-1 β，IL-1 RI和IL-1 RII的表达在不同的炎症性病变在大鼠脑。将IL-1 β注射到脑中以在不存在神经元细胞死亡的情况下产生炎性损伤，而神经元死亡是通过N-甲基-d-天冬氨酸（NMDA）的显微注射特异性诱导的。使用TaqMan RT-PCR和ELISA，我们观察到脑内微量注射IL-1 β后2 h新生IL-1 β合成升高; 24 h后新生IL-1 β仍升高。IL-1 RI mRNA的增加是伴随的，但IL-1 RII mRNA的增加要大得多。免疫组化显示IL-1 RII在脑内皮细胞和浸润的中性粒细胞上表达。相比之下，虽然IL-1 β和IL-1 RI升高到相似的水平，响应于NMDA的挑战，响应延迟和IL-1 RII mRNA的表达是不变的。IL-1受体的病变特异性表达表明，受体的差异调节的方式不直接相关的内源性水平的IL-1在中枢神经系统。
Most pathologies of the brain have an inflammatory component, associated with the release of cytokines such as interleukin-1 beta (IL-1 beta) from resident and infiltrating cells. The IL-1 type I receptor (IL-1RI) initiates a signalling cascade but the type II receptor (IL-1RII) acts as a decoy receptor. Here we have investigated the expression of IL-1 beta, IL-1RI and IL-1RII in distinct inflammatory lesions in the rat brain. IL-1 beta was injected into the brain to generate an inflammatory lesion in the absence of neuronal cell death whereas neuronal death was specifically induced by the microinjection of N-methyl-d-aspartate (NMDA). Using TaqMan RT-PCR and ELISA, we observed elevated de novo IL-1 beta synthesis 2 h after the intracerebral microinjection of IL-1 beta; this de novo IL-1 beta remained elevated 24 h later. There was a concomitant increase in IL-1RI mRNA but a much greater increase in IL-1RII mRNA. Immunostaining revealed that IL-1RII was expressed on brain endothelial cells and on infiltrating neutrophils. In contrast, although IL-1 beta and IL-1RI were elevated to similar levels in response to NMDA challenge, the response was delayed and IL-1RII mRNA expression was unchanged. The lesion-specific expression of IL-1 receptors suggests that the receptors are differentially regulated in a manner not directly related to the endogenous level of IL-1 in the CNS.