The expanding interleukin-1 family and its receptors - Do alternative IL-1 receptor/signaling pathways exist in the brain?
The expanding interleukin-1 family and its receptors - Do alternative IL-1 receptor/signaling pathways exist in the brain?
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DOI：
10.1385/mn:27:3:239
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发表时间：
2003-06-01
影响因子：
5.1
通讯作者：
Pinteaux, E
中科院分区：
文献类型：
--
作者：
Boutin, H;Kimber, I;Pinteaux, E
白细胞介素-1（IL-1）参与神经免疫应答，并在脑中具有多效性作用。令人信服的证据表明，IL-1是炎症和细胞死亡的进展，在脑损伤和脑缺血响应的主要介质。其表达在这些病理条件下强烈增加，并且外源性IL-1的中枢给药显著加剧缺血性脑损伤。相反，抑制IL-1作用（通过脑室内[icv]注射IL-1 ra、IL-1中和抗体或半胱天冬酶-1抑制剂）可显著降低缺血性脑损伤。IL-1通过与IL-1 I型受体（IL-1 RI）结合而起作用，IL-1 RI是迄今为止唯一已知的IL-1的功能性受体。然而，我们最近的研究表明，IL-1可以独立于IL-1 RI发挥作用，这增加了IL-1在大脑中存在其他尚未发现的受体的可能性。近年来对新的IL-1配体和IL-1受体相关分子的研究表明，中枢神经系统（CNS）可能存在IL-1信号通路。
Interleukin-1 (IL-1) has been implicated in neuroimmune responses and has pleiotropic actions in the brain. Compelling evidence has shown that IL-1 is a major mediator of inflammation and the progression of cell death in response to brain injury and cerebral ischemia. Its expression is strongly increased in these pathological conditions, and central administration of exogenous IL-1 significantly exacerbates ischemic brain damage. In contrast, inhibiting IL-1 actions (by intracerebroventricular [icv] injection of IL-1ra, neutralizing antibody to IL-1 or caspase-1 inhibitor) significantly reduces ischemic brain damage. IL-1 acts by binding to the IL-1 type-I receptor (IL-1RI), which is to date, the only known functional receptor for IL-1. However, our recent investigations suggest that IL-1 can act independently of IL-1RI, raising the possibility that additional, as yet undiscovered, receptor(s) for IL-1 exist in the brain. The recent characterization of putative, new IL-1 ligands and new IL-1 receptor-related molecules leads to the hypothesis that there might be alternative IL-1 signaling pathway(s) in the central nervous system (CNS).