S100B binding to RAGE in microglia stimulates COX-2 expression
S100B binding to RAGE in microglia stimulates COX-2 expression
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DOI：
10.1189/jlb.0306198
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发表时间：
2007-01-01
影响因子：
5.5
通讯作者：
Donato, Rosario
中科院分区：
文献类型：
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作者：
Bianchi, Roberta;Adami, Cecilia;Donato, Rosario
除了在星形胶质细胞内发挥调节作用外，EF-HAND类型S100B的钙调节蛋白还被释放到脑细胞外空间，从而影响星形胶质细胞、神经元和小胶质细胞。然而，S100B的细胞外效应是不同的，取决于所获得的浓度和蛋白质对神经元的营养作用，直到纳摩尔浓度，并在微摩尔浓度引起神经元凋亡。S100B对神经元的作用是通过晚期糖基化终产物受体(RAGE)转导的。在高浓度下，S100B还通过与细菌内毒素和干扰素-γ的协同作用，上调小胶质细胞中诱导型一氧化氮合酶的表达，并刺激小胶质细胞释放一氧化氮，从而参与小胶质细胞的激活。我们发现S1100B通过独立地刺激CDC42-rac1-JNK通路和Ras-rac1-NF-kappa B通路，以RAGE依赖的方式上调小胶质细胞中环氧合酶-2的表达。因此，S100B可以看作是一种星形细胞内分泌因子，一旦释放到脑细胞外间隙，可能参与脑损伤过程中的炎症反应。
Besides exerting regulatory roles within astrocytes, the Ca2+-modulated protein of the EF-hand type S100B is released into die brain extracellular space, thereby affecting astrocytes, neurons, and microglia. However, extracellular effects of S100B vary, depending on the concentration attained and the protein being trophic to neurons up to nanomolar concentrations and causing neuronal apoptosis at micromolar concentrations. Effects of S100B on neurons are transduced by receptor for advanced glycation end products (RAGE). At high concentrations, S100B also up-regulates inducible NO synthase in and stimulates NO release by microglia by synergizing with bacterial endotoxin and IFN-gamma, thereby participating in microglia activation. We show here that S1100B up-regulates cyclo-oxygenase-2 expression in microglia in a RAGE-dependent manner in the absence of cofactors through independent stimulation of a Cdc42-Rac1-JNK pathway and a Ras-Rac1-NF-kappa B pathway. Thus, S100B can be viewed as an astrocytic endokine, which might participate in the inflammatory response in the course of brain insults, once liberated into the brain extracellular space.