嗜酸性粒细胞
结肠炎
生物
炎症
癌症研究
偶氮甲烷
癌变
免疫学
CCL11型
炎症性肠病
医学
结直肠癌
癌症
病理
趋化因子
内科学
嗜酸性粒细胞趋化因子
疾病
哮喘
作者
Dina Polosukhina,Kshipra Singh,Mohammad Asim,Daniel P. Barry,Margaret M. Allaman,Dana M. Hardbower,M. Blanca Piazuelo,Mary Kay Washington,Alain P. Gobert,Keith T. Wilson,Lori A. Coburn
出处
期刊:Oncogene
[Springer Nature]
日期:2021-10-08
卷期号:40 (47): 6540-6546
被引量:23
标识
DOI:10.1038/s41388-021-02046-3
摘要
CCL11, also known as eotaxin-1, is described as an eosinophil chemoattractant, which has been implicated in allergic and Th2 inflammatory diseases. We have reported that CCL11 is significantly increased in the serum of inflammatory bowel disease (IBD) patients, colonic eosinophils are increased and correlate with tissue CCL11 levels in ulcerative colitis patients, and CCL11 is increased in dextran sulfate sodium (DSS)-induced murine colitis. Here, we show that CCL11 is involved in the pathogenesis of DSS-induced colitis and in colon tumorigenesis in the azoxymethane (AOM)-DSS model of colitis-associated carcinogenesis (CAC). Ccl11−/− mice exposed to DSS then allowed to recover had significantly less body weight loss and a decrease in histologic injury versus wild-type (WT) mice. In the AOM-DSS model, Ccl11−/− mice exhibited decreased colonic tumor number and burden, histologic injury, and colonic eosinophil infiltration versus WT mice. Ccl11 is expressed by both colonic epithelial and lamina propria immune cells. Studies in bone marrow chimera mice revealed that hematopoietic- and epithelial-cell-derived CCL11 were both important for tumorigenesis in the AOM-DSS model. These findings indicate that CCL11 is important in the regulation of colitis and associated carcinogenesis and thus anti-CCL11 antibodies may be useful for treatment and cancer chemoprevention in IBD.
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