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益生菌治疗通过PI3K/Akt和NOD2表达对沙门氏菌诱导的肠上皮细胞白细胞介素-8反应的不同影响。

The different effects of probiotics treatment on Salmonella-induced interleukin-8 response in intestinal epithelia cells via PI3K/Akt and NOD2 expression.

作者信息

Huang F-C, Huang S-C

机构信息

1 Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123, Ta-pei Road, Niao-Sung District, 833 Kaohsiung, Taiwan ROC.

2 Department of Pathology, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-pei Road, Niao-Sung District, 833 Kaohsiung, Taiwan ROC.

出版信息

Benef Microbes. 2016 Nov 30;7(5):739-748. doi: 10.3920/BM2015.0181. Epub 2016 Sep 29.

Abstract

Salmonella spp. remains a major public health problem for the whole world. Intestinal epithelial cells serve as an essential component of the innate mucosal immune system to defend against Salmonella infection. A substantial amount of evidence has accumulated that probiotics can regulate interleukin 8 (IL-8) involved in innate immunity. However, the exact effect of probiotics on epithelial IL-8 response to Salmonella infection is not well understood. Therefore, we investigated the action of probiotics on Salmonella-infected Caco-2 cells and its novel mechanisms. Two probiotic strains were examined for Salmonella-induced IL-8 responses and regulating proteins using Caco-2 cell cultures. We demonstrated probiotic, either Lactobacillus rhamnosus GG or Bifidobacterium animalis subsp. lactis DSM10140, administered before Salmonella infection conferred significantly suppressive effect on Salmonella-induced IL-8 responses in Caco-2 cells, either in secreted protein or mRNA, via the PI3K/Akt signal pathway while probiotic administered after infection enhanced Salmonella-induced IL-8 responses via nucleotide-binding oligomerisation domain-containing protein 2 expression in membrane. These findings suggest that the different regulation of probiotics on Salmonella-induced IL-8 responses in Caco-2 cells according to the administered timing supports a rationale for the therapeutic use of probiotics in the treatment of Salmonella colitis and inflammatory bowel disease. This can explain the reported controversial effect of probiotics on these diseases.

摘要

沙门氏菌属仍然是全球主要的公共卫生问题。肠道上皮细胞是先天性黏膜免疫系统抵御沙门氏菌感染的重要组成部分。大量证据表明,益生菌可调节参与先天性免疫的白细胞介素8(IL-8)。然而,益生菌对上皮细胞对沙门氏菌感染的IL-8反应的确切影响尚不清楚。因此,我们研究了益生菌对感染沙门氏菌的Caco-2细胞的作用及其新机制。使用Caco-2细胞培养物检测了两种益生菌菌株对沙门氏菌诱导的IL-8反应和调节蛋白的影响。我们证明,在沙门氏菌感染前施用的益生菌,无论是鼠李糖乳杆菌GG还是动物双歧杆菌亚种乳酸亚种DSM10140,通过PI3K/Akt信号通路对Caco-2细胞中沙门氏菌诱导的IL-8反应(无论是分泌蛋白还是mRNA)具有显著的抑制作用,而感染后施用的益生菌则通过膜中含核苷酸结合寡聚化结构域蛋白2的表达增强沙门氏菌诱导的IL-8反应。这些发现表明,益生菌根据施用时间对Caco-2细胞中沙门氏菌诱导的IL-8反应的不同调节,为益生菌在治疗沙门氏菌结肠炎和炎症性肠病中的治疗应用提供了理论依据。这可以解释报道的益生菌对这些疾病的有争议的作用。

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