Extracellular Vesicles Derived from Kefir Grain Lactobacillus Ameliorate Intestinal Inflammation via Regulation of Proinflammatory Pathway and Tight Junction Integrity

被引:60
作者
Kang, Eun Ae [1 ,2 ]
Choi, Hye-In [3 ]
Hong, Seung Wook [4 ,5 ]
Kang, Seokwoo [3 ]
Jegal, Hyeon-Young [3 ]
Choi, Eun Wook [3 ]
Park, Byung-Soon [3 ,6 ]
Kim, Joo Sung [4 ,5 ]
机构
[1] Yonsei Univ, Coll Med, Dept Internal Med, Seoul 03722, South Korea
[2] Yonsei Univ, Coll Med, Inst Gastroenterol, Seoul 03722, South Korea
[3] Prostem Res Inst, Seoul 04778, South Korea
[4] Seoul Natl Univ, Dept Internal Med, Coll Med, Seoul 03080, South Korea
[5] Seoul Natl Univ, Liver Res Inst, Coll Med, Seoul 03080, South Korea
[6] Cellpk Clin, Seoul 06029, South Korea
关键词
extracellular vesicle; Lactobacillus; experimental colitis; tight junction; NF-kappa B; NECROSIS-FACTOR-ALPHA; DEXTRAN SULFATE SODIUM; CYTOKINE PRODUCTION; EPITHELIAL BARRIER; BOWEL-DISEASE; BACTERIA; EXPRESSION; MECHANISM; PATHOGENESIS; INHIBITORS;
D O I
10.3390/biomedicines8110522
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The aim of this study was to demonstrate the anti-inflammatory effect of Lactobacillus kefirgranum PRCC-1301-derived extracellular vesicles (PRCC-1301 EVs) on intestinal inflammation and intestinal barrier function. Human intestinal epithelial cells (IECs) Caco-2 were treated with PRCC-1301 EVs and then stimulated with dextran sulfate sodium (DSS). Real-time RT-PCR revealed that PRCC-1301 EVs inhibited the expression of pro-inflammatory cytokines in Caco-2 cells. PRCC-1301 EVs enhanced intestinal barrier function by maintaining intestinal cell integrity and the tight junction. Loss of Zo-1, claudin-1, and occludin in Caco-2 cells and the colitis tissues was recovered after PRCC-1301 EVs treatment, as evidenced by immunofluorescence analysis. Acute murine colitis was induced using 4% DSS and chronic colitis was generated in piroxicam-treated IL-10(-/-) mice. PRCC-1301 EVs attenuated body weight loss, colon shortening, and histological damage in acute and chronic colitis models in mice. Immunohistochemistry revealed that phosphorylated NF-kappa B p65 and I kappa B alpha were reduced in the colon tissue sections treated with PRCC-1301 EVs. Our results suggest that PRCC-1301 EVs may have an anti-inflammatory effect on colitis by inhibiting the NF-kappa B pathway and improving intestinal barrier function.
引用
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页码:1 / 11
页数:11
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