Artemisinin ameliorates intestinal inflammation by skewing macrophages to the M2 phenotype and inhibiting epithelial–mesenchymal transition,International Immunopharmacology

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Artemisinin ameliorates intestinal inflammation by skewing macrophages to the M2 phenotype and inhibiting epithelial–mesenchymal transition
International Immunopharmacology ( IF 4.8 ) Pub Date : 2020-12-20 , DOI: 10.1016/j.intimp.2020.107284
Manxiu Huai ₁ , Junxiang Zeng ₂ , Wensong Ge ₁

Affiliation

Background

Inflammatory bowel disease (IBD) is a self-destructive intestinal disease whose etiology is unclear but complex and the effective treatment is deficient. Increasing evidences have indicated that immune dysfunction and epithelial–mesenchymal transition (EMT)-related intestinal mucosal barrier impaired hold critical position in the pathogenesis of IBD. Artemisinin (ART) is a sesquiterpenoid compound extracted from Chinese herbal medicine which has good immunomodulatory effects. Studies have shown that artemisinin and its analogues have therapeutic effects on a variety of tumors and immune-related disorders. The purpose of current study was to research the effect and mechanism about artemisinin-induced macrophage polarization to M2 phenotype and inhibiting the process of EMT.

Methods

In vitro, the anti-inflammatory effect of artemisinin is mainly verified by RAW264.7 cells and tissue (colon tissue and PBMC) from CD patients with active intestinal inflammation. RAW264.7 cells stimulated with LPS to induce inflammatory state and ART were used as therapeutic treatment in different concentration. Then the expression levels of pro-inflammatory factors, macrophage polarization and ERK pathway were analyzed. Colon tissue and PBMC from CD patients were treated with ART in different concentrations and macrophage polarization, pro-inflammatory factors expression, EMT-related protein were analyzed. In vivo, DSS-induced colitis mice were treated by ART for seven days. The DAI score was calculated and the colons and spleens were harvested after the animals were sacrificed. The expression of macrophage markers and EMT-related markers in the intestines of mice in each group were monitored by qPCR and western blot.

Result

ART treatment could decrease the levels of pro-inflammatory coefficient expressed in theRAW264.7 cells and human PBMC. Moreover, ART could ameliorate the intestinal inflammation in vivo through down-regulating the expression of pro-inflammatory factors, promoting macrophage polarization to M2 phenotype and inhibiting the process of EMT.

Conclusion

Taken together, our findings demonstrated that artemisinin might ameliorate inflammation by inducing macrophage polarization to M2 phenotype and inhibiting the process of EMT, suggesting that ART may be applied to the rehabilitation of IBD in the future.

中文翻译：

青蒿素通过将巨噬细胞偏向 M2 表型并抑制上皮间质转化来改善肠道炎症

背景

炎症性肠病（IBD）是一种自毁性肠道疾病，其病因尚不清楚但复杂，有效的治疗方法不足。越来越多的证据表明免疫功能障碍和上皮间质转化 (EMT) 相关的肠黏膜屏障受损在 IBD 的发病机制中占有关键地位。青蒿素（ART）是从中草药中提取的倍半萜类化合物，具有良好的免疫调节作用。研究表明，青蒿素及其类似物对多种肿瘤和免疫相关疾病具有治疗作用。本研究的目的是研究青蒿素诱导巨噬细胞极化为M2表型并抑制EMT过程的作用和机制。

方法

在体外，青蒿素的抗炎作用主要通过来自 CD 活动性肠道炎症患者的 RAW264.7 细胞和组织（结肠组织和 PBMC）进行验证。用 LPS 刺激 RAW264.7 细胞以诱导炎症状态和 ART 被用作不同浓度的治疗性处理。然后分析促炎因子、巨噬细胞极化和ERK通路的表达水平。用不同浓度的ART治疗CD患者的结肠组织和PBMC，分析巨噬细胞极化、促炎因子表达、EMT相关蛋白。在体内，由 ART 治疗 DSS 诱导的结肠炎小鼠 7 天。计算 DAI 评分并在处死动物后收获结肠和脾脏。