Expression of interleukin-1 receptors and their role in interleukin-1 actions in murine microglial cells
Expression of interleukin-1 receptors and their role in interleukin-1 actions in murine microglial cells
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DOI：
10.1046/j.1471-4159.2002.01184.x
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发表时间：
2002-11-01
影响因子：
4.7
通讯作者：
Luheshi, GN
中科院分区：
文献类型：
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作者：
Pinteaux, E;Parker, LC;Luheshi, GN
白细胞介素（IL）-1是急性脑损伤和炎症的重要介质，并与慢性神经退行性变有关。中枢神经系统中IL - 1的主要来源是小胶质细胞，它们也被认为是其作用的靶点。然而，没有数据表明IL - 1受体[IL - 1Ⅰ型受体（IL - 1RI）、IL - 1Ⅱ型受体（IL - 1RII）和IL - 1受体辅助蛋白（IL - 1RAcP）]在小胶质细胞上表达。在本研究中，我们研究了小胶质细胞是否表达IL - 1受体，以及它们是否对IL - 1的作用具有靶点或调节特性。逆转录聚合酶链反应（RT - PCR）分析表明，与混合胶质细胞或纯星形胶质细胞培养物相比，小鼠小胶质细胞培养物中IL - 1RI表达较低，IL - 1RII mRNA表达较高。细菌脂多糖（LPS）导致IL - 1RI、IL - 1RII和IL - 1RAcP mRNA表达增加，诱导IL - 1β、IL - 6和前列腺素E₂（PGE₂）释放，并激活小胶质细胞培养物中的核因子κB（NF - κB）和丝裂原活化蛋白激酶（MAPKs）p38以及细胞外信号调节蛋白激酶（ERK1/2），但不激活c - Jun N - 末端激酶（JNK）。相比之下，IL - 1β诱导混合胶质细胞培养物中PGE₂、IL - 6释放并激活NF - κB、p38、JNK和ERK1/2，但在小胶质细胞培养物中未能诱导任何这些反应。IL - 1β也未能影响LPS预处理的小胶质细胞。有趣的是，一种针对IL - 1RII的中和抗体显著增加了LPS处理的小胶质细胞培养基中IL - 1β的浓度，并加剧了混合胶质细胞中IL - 1β诱导的IL - 6释放，这首次证明小胶质细胞的IL - 1RII在脑炎症期间通过结合过量的这种细胞因子来调节IL - 1β的作用。
Interleukin (IL)-1 is an important mediator of acute brain injury and inflammation, and has been implicated in chronic neurodegeneration. The main source of IL-1 in the CNS is microglial cells, which have also been suggested as targets for its action. However, no data exist demonstrating expression of IL-1 receptors [IL-1 type-I receptor (IL-1RI), IL-1 type-II receptor (IL-1RII) and IL-1 receptor accessory protein (IL-1RAcP)] on microglia. In the present study we investigated whether microglia express IL-1 receptors and whether they present target or modulatory properties for IL-1 actions. RT-PCR analysis demonstrated lower expression of IL-1RI and higher expression of IL-1RII mRNAs in mouse microglial cultures compared with mixed glial or pure astrocyte cultures. Bacterial lipopolysaccharide (LPS) caused increased expression of IL-1RI, IL-1RII and IL-1RAcP mRNAs, induced the release of IL-1beta, IL-6 and prostaglandin-E-2 (PGE(2)), and activated nuclear factor kappaB (NF-kappaB) and the mitogen-activated protein kinases (MAPKs) p38, and extracellular signal-regulated protein kinase (ERK1/2), but not c-Jun N-terminal kinase (JNK) in microglial cultures. In comparison, IL-1beta induced the release of PGE(2), IL-6 and activated NF-kappaB, p38, JNK and ERK1/2 in mixed glial cultures, but failed to induce any of these responses in microglial cell cultures. IL-1beta also failed to affect LPS-primed microglial cells. Interestingly, a neutralizing antibody to IL-1RII significantly increased the concentration of IL-1beta in the medium of LPS-treated microglia and exacerbated the IL-1beta-induced IL-6 release in mixed glia, providing the first evidence that microglial IL-1RII regulates IL-1beta actions by binding excess levels of this cytokine during brain inflammation.