Juglone alleviates pneumolysin-induced human alveolar epithelial cell injury via inhibiting the hemolytic activity of pneumolysin

Juglone alleviates pneumolysin-induced human alveolar epithelial cell injury via inhibiting the hemolytic activity of pneumolysin
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Juglone通过抑制肺炎球菌溶血素的溶血活性减轻肺炎球菌溶血素引起的人肺泡上皮细胞损伤

DOI:
10.1007/s10482-017-0880-0
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发表时间:
2017-04
影响因子:
2.6
通讯作者:
Wang Jianfeng
Wang Jianfeng
中科院分区:
生物学3区
文献类型:
--
作者:
Song Meng;Lu Gejin;Li Meng;Deng Xuming;Wang Jianfeng

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肺炎链球菌(简称肺炎球菌)是一种条件致病菌,可引起多种人类疾病,包括急性中耳炎、肺炎、败血症和细菌性脑膜炎,具有多种与肺炎球菌感染和致病相关的毒力因子。溶气素(PLY)具有在富含胆固醇的膜上形成孔的能力,是OFS的关键毒力因子。肺炎,在肺炎球菌感染过程中会造成严重的组织损伤。核桃仁酮(Juglone,JG)是一种天然的1,4-萘醌,广泛存在于核桃树的根、叶、木材和果实中,通过抑制PLY的寡聚化来抑制PLY诱导的溶血,并表现出最低限度的抗S。肺炎活动性。此外,当人肺泡上皮细胞(A549)与PLY和JG共同培养时,PLY介导的细胞损伤明显减轻。这些结果表明,JG可直接与PLE相互作用,从而降低毒素对人肺泡上皮细胞的细胞毒性。因此,健肺颗粒是一种有效的PLY抑制剂,可保护肺细胞免受PLY介导的细胞损伤。本研究也为开发治疗OFS的抗毒力药物提供了依据。肺炎感染。
Streptococcus pneumoniae(the pneumococcus) is an opportunistic pathogen responsible for several human diseases, including acute otitis media, pneumonia, sepsis and bacterial meningitis, and possesses numerous virulence factors associated with pneumococcal infection and pathogenesis. With the capacity to form pores in cholesterol-rich membranes, pneumolysin (PLY) is a key virulence factor ofS. pneumoniaeand causes severe tissue damage during pneumococcal infection. Juglone (JG), a natural 1,4-naphthoquinone widely found in the roots, leaves, woods and fruits ofJuglandaceaewalnut trees, inhibits PLY-induced hemolysis via inhibition of the oligomerization of PLY and exhibits minimal anti-S. pneumoniaeactivity. In addition, when human alveolar epithelial (A549) cells were co-cultured with PLY and JG, PLY-mediated cell injury was significantly alleviated. These results indicate that JG directly interacts with PLY to reduce the cytotoxicity of the toxin in human alveolar epithelial cells. Hence, JG is an effective inhibitor of PLY and protects lung cells from PLY-mediated cell injury. This study also provides the basis for the development of anti-virulence drugs for the treatment ofS. pneumoniaeinfections.
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