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在 DSS 诱导的结肠炎模型中,一种寄生虫蛋白的免疫保护作用。

Immune Protection of a Helminth Protein in the DSS-Induced Colitis Model in Mice.

机构信息

Department of Parasitology, Medical College of Zhengzhou University, Zhengzhou, China.

Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States.

出版信息

Front Immunol. 2021 Apr 29;12:664998. doi: 10.3389/fimmu.2021.664998. eCollection 2021.

Abstract

Inflammatory bowel disease (IBD) increases the risk of colorectal cancer, and it has the potential to diminish the quality of life. Recent clinical and experimental evidence demonstrate protective aspects of parasitic helminth infection against IBD. Reports have highlighted the potential use of helminths and their byproducts as potential treatment for IBD. In the current study, we studied the effect of a newborn larvae-specific serine protease from (TsSp) on the host immune and inflammatory responses. A 49-kDa recombinant TsSp (rTsSp) was expressed in BL21 (DE3) and purified. The cytotoxicity of rTsSp was analyzed. The immune protective effect of rTsSp was studied by using dextran sodium sulfate (DSS)-induced mouse colitis model. The result illustrated that rTsSp has no toxic effects on cells. We further demonstrated that administration of the rTsSp without the additional adjuvant before the induction of DSS-induced colitis reduced the severity of intestinal inflammation and the disease index; it suppressed macrophage infiltration, reduced TNF-α secretion, and induced IL-10 expression. Our findings suggest therapeutic potential of rTsSp on colitis by altering the effect of macrophages. Data also suggest immunotherapy with rTsSp holds promise for use as an additional strategy to positively modulate inflammatory processes involved in IBD.

摘要

炎症性肠病 (IBD) 会增加结直肠癌的风险,并且有可能降低生活质量。最近的临床和实验证据表明寄生虫蠕虫感染对 IBD 具有保护作用。有报道强调了蠕虫及其产物作为 IBD 潜在治疗方法的潜在用途。在本研究中,我们研究了一种来自 (TsSp)的新生幼虫特异性丝氨酸蛋白酶对宿主免疫和炎症反应的影响。在 BL21 (DE3) 中表达并纯化了 49 kDa 的重组 TsSp (rTsSp)。分析了 rTsSp 的细胞毒性。使用葡聚糖硫酸钠 (DSS) 诱导的小鼠结肠炎模型研究了 rTsSp 的免疫保护作用。结果表明 rTsSp 对细胞没有毒性作用。我们进一步证明,在诱导 DSS 诱导的结肠炎之前,给予 rTsSp 而不添加额外的佐剂可减轻肠道炎症和疾病指数的严重程度;它抑制巨噬细胞浸润,减少 TNF-α 的分泌,并诱导 IL-10 的表达。我们的研究结果表明 rTsSp 通过改变巨噬细胞的作用对结肠炎具有治疗潜力。数据还表明,rTsSp 的免疫疗法有望作为一种额外的策略,积极调节 IBD 中涉及的炎症过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99f2/8117093/d23e78f19b9f/fimmu-12-664998-g001.jpg

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