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幽门螺杆菌感染减少 AOM/DSS 诱导的结肠炎相关癌症小鼠模型中的 TAMs 浸润。

Helicobacter pylori infection reduces TAMs infiltration in a mouse model of AOM/DSS induced colitis-associated cancer.

机构信息

Department of Gastroenterology, Peking University First Hospital, Beijing, China.

出版信息

PLoS One. 2020 Nov 17;15(11):e0241840. doi: 10.1371/journal.pone.0241840. eCollection 2020.

DOI:10.1371/journal.pone.0241840
PMID:33201893
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7671535/
Abstract

Inflammatory bowel disease (IBD) increases the risk of colitis-associated cancer (CAC). Evidences suggest that Helicobacter pylori (H. pylori) infection is associated with a low risk of IBD and protects against experimental colitis in mouse models. However, the effect of H. pylori infection in CAC remains unclear. We previously reported that H. pylori infection increased M2 macrophages in dextran sodium sulfate (DSS)-induced chronic colitis. Tumor-associated macrophages (TAMs) play a pivotal role in colon cancer. Therefore, we established a H. pylori-infected CAC mouse model induced by azoxymethane and DSS to explore the effect of H. pylori infection on TAMs in CAC. Here, we demonstrated that H. pylori infection attenuated the development of CAC by decreasing tumor multiplicity, tumor size, tumor grade and colitis scores. Moreover, H. pylori infection reduced the infiltration of TAMs, particularly M2-like TAMs in CAC tumors, accompanied with the down-regulated pro-inflammatory and pro-tumorigenic factors TNF-α, IL-1β, IL-6 and IL-23 in tumors of CAC mice. Our study suggests that H. pylori infection can reduce TAMs infiltration and regulate cytokines expression in CAC.

摘要

炎症性肠病(IBD)会增加结肠炎相关癌症(CAC)的风险。有证据表明,幽门螺杆菌(H. pylori)感染与 IBD 的低风险相关,并可防止小鼠模型中的实验性结肠炎。然而,H. pylori 感染对 CAC 的影响尚不清楚。我们之前报道过,H. pylori 感染会增加葡聚糖硫酸钠(DSS)诱导的慢性结肠炎中的 M2 巨噬细胞。肿瘤相关巨噬细胞(TAMs)在结肠癌中发挥关键作用。因此,我们建立了一种由氧化偶氮甲烷和 DSS 诱导的 H. pylori 感染 CAC 小鼠模型,以探讨 H. pylori 感染对 CAC 中 TAMs 的影响。在这里,我们证明 H. pylori 感染通过降低肿瘤数量、肿瘤大小、肿瘤分级和结肠炎评分来减轻 CAC 的发展。此外,H. pylori 感染减少了 TAMs 的浸润,特别是 CAC 肿瘤中的 M2 样 TAMs,同时伴有肿瘤中促炎和促肿瘤因子 TNF-α、IL-1β、IL-6 和 IL-23 的下调。我们的研究表明,H. pylori 感染可以减少 CAC 中 TAMs 的浸润并调节细胞因子的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2094/7671535/51f1750d4df1/pone.0241840.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2094/7671535/6653f082cbf3/pone.0241840.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2094/7671535/c616cf5705e7/pone.0241840.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2094/7671535/a49b38d5faab/pone.0241840.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2094/7671535/b3387eda6d9c/pone.0241840.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2094/7671535/51f1750d4df1/pone.0241840.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2094/7671535/6653f082cbf3/pone.0241840.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2094/7671535/c616cf5705e7/pone.0241840.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2094/7671535/a49b38d5faab/pone.0241840.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2094/7671535/b3387eda6d9c/pone.0241840.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2094/7671535/51f1750d4df1/pone.0241840.g005.jpg

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