Neurologische Klinik, Universitätsklinikum Heidelberg, Heidelberg, Germany.
J Neurosci Res. 2010 Jan;88(1):16-23. doi: 10.1002/jnr.22185.
Previous studies have shown that activin A, a neuroprotective cytokine and dimeric polypeptide composed of two betaA subunits, is elevated in the cerebrospinal fluid of patients suffering from bacterial meningitis. In this study, to elucidate further the functional significance and pathophysiological implications of these findings, we demonstrated that microglial cells are not only the source but also the target cells of activin A in the central nervous system: immunohistochemistry and RT-PCR revealed expression of activin subunit betaA mRNA as well as activin receptor type I and type II mRNA in rat microglia in vitro. Further studies showed that activin enhances microglial proliferation and decreases the gamma-interferon-induced synthesis of nitric oxide, one of several microglial mediators involved in the inflammatory response in microglia activation. Furthermore, quantitative RT-PCR, Western blotting, and ELISA showed an inhibitory effect of activin on inducible nitric oxide synthase, tumor necrosis factor-alpha, interleukin-6, and interleukin-1beta gene and protein levels after lipopolysaccharide treatment. We suggest that the increased synthesis of activin A is directly involved, via influence on microglia cell functions, in the modulation of the inflammatory response in bacterial meningitis.
先前的研究表明，激活素 A 是一种神经保护细胞因子，也是由两个βA 亚基组成的二聚多肽，在患有细菌性脑膜炎的患者的脑脊液中升高。在这项研究中，为了进一步阐明这些发现的功能意义和病理生理意义，我们证明了小胶质细胞不仅是中枢神经系统中激活素 A 的来源细胞，也是其靶细胞：免疫组织化学和 RT-PCR 显示了大鼠小胶质细胞中激活素亚基βA mRNA 以及激活素受体 I 型和 II 型 mRNA 的表达。进一步的研究表明，激活素增强小胶质细胞的增殖，并减少 γ-干扰素诱导的一氧化氮合成，一氧化氮是几种小胶质细胞介体之一，参与小胶质细胞激活中的炎症反应。此外，定量 RT-PCR、Western 印迹和 ELISA 显示，激活素对脂多糖处理后诱导型一氧化氮合酶、肿瘤坏死因子-α、白细胞介素-6 和白细胞介素-1β基因和蛋白水平具有抑制作用。我们认为，激活素 A 合成的增加通过影响小胶质细胞的功能，直接参与了细菌性脑膜炎中炎症反应的调节。
