Recruitment of M1 Macrophages May Not Be Critical for Protection against Colitis-Associated Tumorigenesis

International Journal of Molecular Sciences

Luis I. Terrazas¹  Elizabeth Garduño-Javier¹  Felipe Vaca-Paniagua¹  Stephanie Guerrero-García¹  Jossael A. Espinosa¹  Itzel Medina-Andrade¹  Victoria Hernández-Gómez¹  Miriam Rodríguez-Sosa¹  Jonadab E. Olguín¹ 

[1] Laboratorio Nacional en Salud FES-Iztacala, Universidad Nacional Autónoma de México, Av. De los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, Estado de México, Mexico;

关键词: colitis-associated colon cancer;    inflammation;    IL4Rα;    macrophages;   

DOI  :  10.3390/ijms222011204

来源: DOAJ

【 摘 要 】

A close connection between inflammation and the risk of developing colon cancer has been suggested in the last few years. It has been estimated that patients diagnosed with some types of inflammatory bowel disease, such as ulcerative colitis or Crohn’s disease, have up to a 30% increased risk of developing colon cancer. However, there is also evidence showing that the activation of anti-inflammatory pathways, such as the IL-4 receptor-mediated pathway, may favor the development of colon tumors. Using an experimental model of colitis-associated colon cancer (CAC), we found that the decrease in tumor development in global IL4Rα knockout mice (IL4RαKO) was apparently associated with an inflammatory response mediated by the infiltration of M1 macrophages (F480⁺TLR2⁺STAT1⁺) and iNOS expression in colon tissue. However, when we developed mice with a specific deletion of IL4Rα in macrophages (LysMcreIL4Rα^−/lox mice) and subjected them to CAC, it was found that despite presenting a large infiltration of M1 macrophages into the colon, these mice were as susceptible to colon-tumorigenesis as WT mice. These data suggest that in the tumor microenvironment the absence of IL4Rα expression on macrophages, as well as the recruitment of M1 macrophages, may not be directly associated with resistance to developing colon tumors. Therefore, it is possible that IL4Rα expression in other cell types, such as colonic epithelial cells, could have an important role in promoting the development of colitis-associated colon tumorigenesis.

【 授权许可】

Unknown