抗菌肽
微生物学
生物
先天免疫系统
脂多糖
抗菌剂
免疫系统
脑膜
肺炎链球菌
脑膜炎
炎症
肿瘤坏死因子α
免疫学
医学
抗生素
神经科学
精神科
作者
Lars‐Ove Brandenburg,Deike Varoga,Nicoletta Nicolaeva,Stephen L. Leib,Rainer Podschun,Christoph Jan Wruck,Henrik Wilms,Ralph Lucius,Thomas Pufe
标识
DOI:10.1016/j.jneuroim.2009.10.004
摘要
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.
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