Kang Eun Ae, Choi Hye-In, Hong Seung Wook, Kang Seokwoo, Jegal Hyeon-Young, Choi Eun Wook, Park Byung-Soon, Kim Joo Sung
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea.
Prostemics Research Institute, Seoul 04778, Korea.
Biomedicines. 2020 Nov 20;8(11):522. doi: 10.3390/biomedicines8110522.
The aim of this study was to demonstrate the anti-inflammatory effect of 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-κB p65 and IκBα 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-κB pathway and improving intestinal barrier function.
本研究的目的是证明PRCC - 1301衍生的细胞外囊泡（PRCC - 1301 EVs）对肠道炎症和肠道屏障功能的抗炎作用。用人肠道上皮细胞（IECs）Caco - 2 进行PRCC - 1301 EVs处理，然后用葡聚糖硫酸钠（DSS）刺激。实时逆转录聚合酶链反应（Real - time RT - PCR）显示，PRCC - 1301 EVs抑制了Caco - 2细胞中促炎细胞因子的表达。PRCC - 1301 EVs通过维持肠道细胞完整性和紧密连接增强了肠道屏障功能。免疫荧光分析表明，PRCC - 1301 EVs处理后，Caco - 2细胞和结肠炎组织中紧密连接蛋白1（Zo - 1）、闭合蛋白1（claudin - 1）和闭锁蛋白（occludin）的缺失得以恢复。使用4% DSS诱导急性小鼠结肠炎，并在吡罗昔康处理的白细胞介素10（IL - 10）小鼠中诱发慢性结肠炎。PRCC - 1301 EVs减轻了小鼠急性和慢性结肠炎模型中的体重减轻、结肠缩短和组织学损伤。免疫组织化学显示，PRCC - 1301 EVs处理的结肠组织切片中磷酸化的核因子κB p65（NF - κB p65）和IκBα减少。我们的结果表明，PRCC - 1301 EVs可能通过抑制NF - κB途径和改善肠道屏障功能对结肠炎具有抗炎作用。
