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早期生长反应因子-2(Egr-2)在脂多糖诱导的神经炎症中的作用。

Involvement of early growth response-2 (Egr-2) in lipopolysaccharide-induced neuroinflammation.

机构信息

Department of Neurology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.

出版信息

J Mol Histol. 2013 Jun;44(3):249-57. doi: 10.1007/s10735-013-9482-y. Epub 2013 Jan 11.

Abstract

Early growth response-2 (Egr-2) protein is a transcription factor, which belongs to Egr family which involve in modulating the peripheral immune response, by means of the induction of differentiation of lymphocyte precursors, activation of T and B cells. Egr-2 plays essential roles in peripheral nerve myelination, adipogenesis, tissue repair and fibrosis, immune tolerance; however, its regulation and role in central nervous system (CNS) remain poorly understood. In contrast to Egr-1, which has been extensively investigated, the regulation and function of Egr-2 remains less well characterized. To elaborate whether Egr-2 was involved in CNS injury, we performed a neuroinflammatory model by lipopolysaccharide (LPS) lateral ventral injection in adult rats. Egr-2 expression was strongly induced in active glia cells (astrocytes and microglias) in inflamed brain cortex. In vitro studies indicated that the upregulation of Egr-2 may be involved in the subsequent glia cellular activation following LPS exposure; and knock down of Egr-2 in primary mixed glial cultures (MGC) by siRNA showed that Egr-2 promoted the synthesis of TNF-α. Collectively, these results suggested Egr-2 may be important in host defense in CNS immune response, which might provide a potential target to the treatment of neuroinflammation.

摘要

早期生长反应-2(Egr-2)蛋白是一种转录因子,属于 Egr 家族,可通过诱导淋巴细胞前体的分化、T 和 B 细胞的激活来调节外周免疫反应。Egr-2 在周围神经髓鞘形成、脂肪生成、组织修复和纤维化、免疫耐受中发挥重要作用;然而,其在中枢神经系统(CNS)中的调控和作用仍知之甚少。与广泛研究的 Egr-1 不同,Egr-2 的调控和功能尚未得到充分描述。为了阐明 Egr-2 是否参与中枢神经系统损伤,我们通过脂多糖(LPS)侧腹侧注射在成年大鼠中建立了神经炎症模型。Egr-2 在炎症大脑皮层的活性神经胶质细胞(星形胶质细胞和小胶质细胞)中强烈诱导表达。体外研究表明,Egr-2 的上调可能参与 LPS 暴露后随后的神经胶质细胞激活;并通过 siRNA 在原代混合神经胶质培养物(MGC)中敲低 Egr-2 表明,Egr-2 促进 TNF-α 的合成。总之,这些结果表明 Egr-2 可能在中枢神经系统免疫反应中的宿主防御中很重要,这可能为神经炎症的治疗提供一个潜在的靶点。

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