Expression and regulation of antimicrobial peptide rCRAMP after bacterial infection in primary rat meningeal cells
Expression and regulation of antimicrobial peptide rCRAMP after bacterial infection in primary rat meningeal cells
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DOI：
10.1016/j.jneuroim.2009.10.004
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发表时间：
2009-12-10
影响因子：
3.3
通讯作者：
Pufe, Thomas
中科院分区：
文献类型：
--
作者：
Brandenburg, Lars-Ove;Varoga, Deike;Pufe, Thomas
细菌性脑膜炎的特征是脑膜发炎，并且仍然是死亡和发病的重要原因。脑膜细胞覆盖在大脑表面，参与病原体与大脑之间的第一次相互作用。关于脑膜细胞的作用和抗菌肽在先天性免疫系统中的表达，人们知之甚少。在本研究中，我们研究了与人IL-37同源物--大鼠鞘蛋白相关抗菌肽(RCRAMP)在大鼠脑膜细胞中的表达、分泌和杀菌特性，以及与不同细菌上清液和细菌细胞壁成分脂多糖(LPS)和肽聚糖(PGN)的作用。通过琼脂扩散试验，我们观察到脑膜细胞上清液与细菌上清液、内毒素和PGN孵育后显示出抗菌活性的迹象。用siRNA抑制rCRAMP的表达降低了细胞培养上清液的抗菌活性。RCRAMP在大鼠脑膜细胞中的表达涉及多种信号转导途径，由炎性细胞因子IL-1、-6和肿瘤坏死因子α诱导。在一种实验性脑膜炎模型中，新生大鼠脑池内感染肺炎链球菌，免疫组织化学方法将rCRAMP定位于脑膜细胞。这些结果表明，脑膜细胞产生的盲肠毒素在中枢神经系统细菌感染中对病原体的天然免疫反应中起重要作用。(C)2009爱思唯尔B.V.保留所有权利。
Bacterial meningitis is characterized by an inflammation of the meninges and continues to be an important cause of mortality and morbidity. Meningeal cells cover the cerebral surface and are involved in the first interaction between pathogens and the brain. Little is known about the role of meningeal cells and the expression of antimicrobial peptides in the innate immune system. In this study we characterized the expression, secretion and bactericidal properties of rat cathelin-related antimicrobial peptide (rCRAMP), a homologue of the human LL-37, in rat meningeal cells after incubation with different bacterial supernatants and the bacterial cell wall components lipopolysaccharide (LPS) and peptidoglycan (PGN). Using an agar diffusion test, we observed that supernatants from meningeal cells incubated with bacterial supernatants, LPS and PGN showed signs of antimicrobial activity. The inhibition of rCRAMP expression using siRNA reduced the antimicrobial activity of the cell culture supernatants. The expression of rCRAMP in rat meningeal cells involved various signal transduction pathways and was induced by the inflammatory cytokines interleukin-1, -6 and tumor necrosis factor alpha. In an experimental model of meningitis, infant rats were intracisternally infected with Streptococcus pneumoniae and rCRAMP was localized in meningeal cells using immunohistochemistry. These results suggest that cathelicidins produced by meningeal cells play an important part in the innate immune response against pathogens in CNS bacterial infections. (C) 2009 Elsevier B.V. All rights reserved.