Regulation of expression of the novel IL-1 receptor family members in the mouse brain
Regulation of expression of the novel IL-1 receptor family members in the mouse brain
复制标题
DOI：
10.1111/j.1471-4159.2005.03364.x
复制
发表时间：
2005-10-01
影响因子：
4.7
通讯作者：
Rothwell, NJ
中科院分区：
文献类型：
--
作者：
Andre, R;Lerouet, D;Rothwell, NJ
细胞因子的白细胞介素-1（IL-1）家族的成员是响应于对脑的急性和慢性损伤的宿主防御反应和炎症发展的调节中的关键介质。两种主要的激动剂IL-1 α和IL-1 β与由1型IL-1受体（IL-1 RI）和辅助蛋白（IL-1 RAcP）组成的膜受体复合物结合。IL-1受体超家族的新孤儿成员（包括ST 2/T1、IL-1 Rrp 2、TIGIRR 1和-2、SIGGIR、IL-18 R α和IL-18 R β）的发现增加了对脑中存在替代性IL-1配体信号传导途径的推测。我们在这里证明，所有IL-1 R样孤儿受体都由许多脑细胞类型表达，包括星形胶质细胞、小胶质细胞、少突胶质祖细胞和神经元。IL-18 R β表达在体外对用细菌脂多糖（LPS）处理混合胶质细胞的反应中显著增加，而IL-1 Rrp 2和TIGIRR 1的表达降低。此外，IL-18 R β、IL-1 Rrp 2，而不是TIGIRR 1表达，在体内脑中响应于LPS的外周施用或大脑中动脉闭塞（MCA）而增加。这些结果表明，新发现的IL-1受体家族成员在中枢神经系统疾病中的可能作用。
Members of the interleukin-1 (IL-1) family of cytokines are key mediators in the regulation of host defence responses and the development of inflammation in response to acute and chronic injury to the brain. Two major agonists, IL-1 alpha and IL-1 beta, bind to a membrane receptor complex composed of the type-1 IL-1 receptor (IL-1RI) and the accessory protein (IL-1RAcP). The discovery of new orphan members of the IL-1 receptor superfamily (including ST2/T1, IL-1Rrp2, TIGIRR1 and -2, SIGGIR, IL-18R alpha and IL-18R beta) has increased speculation that alternative IL-1 ligands signalling pathways exist in the brain. We demonstrate here that all the IL-1R-like orphan receptors are expressed by many brain cell types including astrocytes, microglia, oligodendrocytic progenitor cells and neurons. IL-18R beta expression was significantly increased in response to treatment of mixed glia with bacterial lipopolysaccharide (LPS) in vitro, whereas expression of IL-1Rrp2 and TIGIRR1 was reduced. Furthermore, IL-18R beta, IL-1Rrp2, but not TIGIRR1 expression, was increased in the brain in vivo in response to peripheral administration of LPS or middle cerebral artery occlusion (MCA). These results suggest possible roles for newly identified members of the IL-1 receptor family in CNS diseases.