Aronica Eleonora, Gorter Jan A, Rozemuller Annemieke J, Yankaya Bulent, Troost Dirk
Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, Meibergdreef 9 1105 AZ Amsterdam, The Netherlands.
J Neuroimmunol. 2005 Mar;160(1-2):188-94. doi: 10.1016/j.jneuroim.2004.11.015. Epub 2005 Jan 21.
Expression of metabotropic glutamate receptor 5 (mGluR5) protein is known to be plastic and to depend critically on the astrocytes' microenvironment. In the present study we investigated whether interleukins, which are involved in the immune response following brain injury, could contribute to the regulation of mGluR5 protein in human astrocytes in culture. Using Western blotting and immunocytochemistry, no detectable changes in the expression of the mGluR5 protein were observed with both interleukin 1beta and interleukin 6 in undifferentiated cultures (growing in serum free media). In contrast, in cultures that had been morphologically differentiated by exposure to epidermal growth factor (EGF), addition of interleukin 1beta (but not interleukin 6) reduced mGluR5 protein expression. In addition, stimulation of phosphoinositide hydrolysis by the selective group I agonist (S)-3,5-dihydroxyphenylglycine (DHPG) was reduced after exposure to interleukin 1beta. The suppressive effect on mGluR5 was prevented by the interleukin 1 receptor antagonist. Thus, interleukin 1beta may represent an additional pathway through which mGluR5 expression and function can be modulated in astrocytes under different pathological conditions associated with an inflammatory response.
已知代谢型谷氨酸受体5（mGluR5）蛋白的表达具有可塑性，并且严重依赖于星形胶质细胞的微环境。在本研究中，我们调查了参与脑损伤后免疫反应的白细胞介素是否有助于调节培养的人星形胶质细胞中mGluR5蛋白的表达。使用蛋白质印迹法和免疫细胞化学方法，在未分化的培养物（在无血清培养基中生长）中，白细胞介素1β和白细胞介素6均未观察到mGluR5蛋白表达的可检测变化。相反，在通过暴露于表皮生长因子（EGF）进行形态学分化的培养物中，添加白细胞介素1β（而非白细胞介素6）可降低mGluR5蛋白表达。此外, 在暴露于白细胞介素1β后，选择性I组激动剂（S）-3,5-二羟基苯甘氨酸（DHPG）对磷酸肌醇水解的刺激作用降低。白细胞介素1受体拮抗剂可阻止对mGluR5的抑制作用。因此，白细胞介素1β可能代表了在与炎症反应相关的不同病理条件下，星形胶质细胞中mGluR5表达和功能可被调节的另一条途径。
