低剂量矢车菊素-3-O-葡萄糖苷通过 CD169+巨噬细胞途径缓解葡聚糖硫酸钠诱导的结肠炎。

Low Dose of Cyanidin-3-O-Glucoside Alleviated Dextran Sulfate Sodium-Induced Colitis, Mediated by CD169+ Macrophage Pathway.

机构信息

Department of Cell Biology, School of Basic Medical Science, Shandong University, Jinan, Shandong, China.

Department of Food Science and Engineering, Institute of Food Safety and Nutrition, Guangdong Engineering Technology Center of Food Safety Molecular Rapid Detection, Jinan University, Guangzhou, China.

出版信息

Inflamm Bowel Dis. 2019 Aug 20;25(9):1510-1521. doi: 10.1093/ibd/izz090.

DOI:10.1093/ibd/izz090

PMID:31107535

Abstract

BACKGROUND

Inflammatory bowel disease (IBD) is a chronic disease of the intestinal tract in which excessive activation of inflammatory response is correlated. Cyanidin-3-O-glucoside (C3G) is a powerful anti-inflammatory agent, widely existing in fruits and vegetables. However, the role of C3G has rarely been investigated in dextran sulfate sodium (DSS)-induced colitis.

METHODS

In an attempt to elucidate the possible mechanism of IBD and develop new efficient therapeutic methods for colitis, we evaluated the effects of C3G on DSS-induced colitis. DSS-induced colitic C57BL/6 mice were intraperitoneal injected with 1ug C3G or phosphate buffer every 2 days, a total of 3 times; the changes in macrophages and regular T cells were analyzed by flow cytometry and immunofluorescence. Cytokines and chemokines were measured by real-time quantitative polymerase chain reaction.

RESULTS

The results showed that C3G treatment did not cause changes in body weight and colon length as much as those of DSS-treated mice only. Cytokine expression levels such as interleukin (IL)- 6, IL-1β, IL-18, tumor necrosis factor α, interferon γ (IFN γ) in colons and mesenteric lymph nodes (mLNs) from C3G-treated mice were lower than those from colitic mice. Meanwhile, C3G injection inhibited the decrease in CCL22 levels and Tregs induction in colitic mice. Furthermore, the activation of macrophages by LPS and increase of CD169+ cells induced by type I IFN could be inhibited by C3G directly in vitro.

CONCLUSIONS

The study is the first to demonstrate strong effects of C3G to alleviate DSS-induced colonic damage in mice. The effect of C3G on DSS-induced colitis clearly showed a decrease of CD169+ macrophages in both the colon and mLNs. An increase of CD169+ cells induced by type I IFN could be inhibited by C3G. All these data suggest that the role of C3G in colitic inflammation was mediated at least partially by CD169+ cells and the type I IFN pathway.

摘要

背景

炎症性肠病（IBD）是一种肠道慢性疾病，其中炎症反应过度激活与疾病相关。矢车菊素-3-O-葡萄糖苷（C3G）是一种强大的抗炎剂，广泛存在于水果和蔬菜中。然而，C3G 在葡聚糖硫酸钠（DSS）诱导的结肠炎中的作用很少被研究。

方法

为了阐明 IBD 的可能机制并开发治疗结肠炎的新有效方法，我们评估了 C3G 对 DSS 诱导的结肠炎的影响。用 DSS 诱导结肠炎的 C57BL/6 小鼠腹腔内每 2 天注射 1μg C3G 或磷酸盐缓冲液，共 3 次；通过流式细胞术和免疫荧光分析巨噬细胞和常规 T 细胞的变化。通过实时定量聚合酶链反应测量细胞因子和趋化因子。

结果

结果表明，C3G 处理并未像 DSS 处理的小鼠那样引起体重和结肠长度的明显变化。来自 C3G 处理小鼠的结肠和肠系膜淋巴结（mLNs）中白细胞介素（IL）-6、IL-1β、IL-18、肿瘤坏死因子-α、干扰素γ（IFNγ）等细胞因子的表达水平低于结肠炎小鼠。同时，C3G 注射抑制了结肠炎小鼠 CCL22 水平的降低和 Treg 的诱导。此外，C3G 可直接在体外抑制 LPS 激活的巨噬细胞和 I 型 IFN 诱导的 CD169+细胞的增加。

结论

本研究首次证明 C3G 可有效缓解 DSS 诱导的小鼠结肠损伤。C3G 对 DSS 诱导的结肠炎的作用在结肠和 mLNs 中均明显降低 CD169+巨噬细胞。I 型 IFN 诱导的 CD169+细胞的增加可被 C3G 抑制。所有这些数据表明，C3G 在结肠炎炎症中的作用至少部分是通过 CD169+细胞和 I 型 IFN 途径介导的。