IL-4 down-regulates lipopolysaccharide-induced formyl peptide receptor 2 in murine microglial cells by inhibiting the activation of mitogen-activated protein kinases
IL-4 down-regulates lipopolysaccharide-induced formyl peptide receptor 2 in murine microglial cells by inhibiting the activation of mitogen-activated protein kinases
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DOI：
10.4049/jimmunol.171.10.5482
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发表时间：
2003-11-15
影响因子：
4.4
通讯作者：
Wang, JM
中科院分区：
文献类型：
--
作者：
Iribarren, P;Cui, YH;Wang, JM
小胶质细胞积极参与中枢神经系统的促炎症反应。在细菌 LPS 刺激下，小胶质细胞表达功能性甲酰基肽受体 2，该受体介导多种多肽激动剂的趋化和激活作用，包括淀粉样蛋白 β (Abeta(1-42))（阿尔茨海默病的关键致病因子）。在本研究中，我们发现LPS诱导的小胶质细胞中甲酰基肽受体2的表达和功能被Th2型细胞因子IL-4显着抑制。我们努力阐明其机制基础，结果表明，IL-4 可减弱 LPS 刺激的 NF-κB、细胞外信号调节激酶和 p38 丝裂原激活蛋白激酶的激活，并且 IL-4 的作用与磷酸肌醇 3 激酶途径依赖性丝氨酸/苏氨酸磷酸酶活性增加有关。这些结果表明，IL-4可能在维持中枢神经系统稳态和调节以响应促炎刺激物的小胶质细胞激活为特征的疾病过程中发挥重要作用。
Microglial cells actively participate in proinflammatory responses in the CNS. Upon stimulation with the bacterial LPS, microglial cells express a functional formyl peptide receptor 2 which mediates the chemotactic and activating effects of a variety of polypeptide agonists including amyloid beta (Abeta(1-42)), a critical pathogenic agent in Alzheimer's disease. In the present study, we found that LPS-induced expression and function of formyl peptide receptor 2 in microglial cells was markedly inhibited by IL-4, a Th2-type cytokine. Our effort to elucidate the mechanistic basis revealed that IL-4 attenuated LPS-stimulated activation of NF-kappaB, extracellular signal-regulated kinase, and p38 mitogen-activated protein kinase, and the effect of IL-4 was associated with a phosphoinositide 3-kinase pathway-dependent increase in serine/threonine phosphatase activity. These results suggest that IL-4 may play an important role in the maintenance of homeostasis of CNS and in the regulation of the disease process characterized by microglial activation in response to proinflammatory stimulants.