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


Por: Medina-Andrade, Itzel, Olguin, Jonadab E., Guerrero-Garcia, Stephanie, Espinosa, Jossael A., Garduño-Javier E., Hernandez-Gomez, Victoria, Vaca-Paniagua, Felipe, Rodriguez-Sosa, Miriam, Terrazas, Luis I.

Publicada: 1 oct 2021
Resumen:
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 IL4R alpha knockout mice (IL4R alpha KO) 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 IL4R alpha in macrophages (LysMcreIL4R alpha(-/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 IL4R alpha 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 IL4R alpha expression in other cell types, such as colonic epithelial cells, could have an important role in promoting the development of colitis-associated colon tumorigenesis.



Filiaciones:
Medina-Andrade, Itzel:
 Laboratorio Nacional en Salud FES-Iztacala, Universidad Nacional Autónoma de México, Av. De los Barrios 1, Los Reyes Iztacala, Tlalnepantla, Estado de México, 54090, Mexico

Olguin, Jonadab E.:
 Laboratorio Nacional en Salud FES-Iztacala, Universidad Nacional Autónoma de México, Av. De los Barrios 1, Los Reyes Iztacala, Tlalnepantla, Estado de México, 54090, Mexico

Guerrero-Garcia, Stephanie:
 Laboratorio Nacional en Salud FES-Iztacala, Universidad Nacional Autónoma de México, Av. De los Barrios 1, Los Reyes Iztacala, Tlalnepantla, Estado de México, 54090, Mexico

Espinosa, Jossael A.:
 Laboratorio Nacional en Salud FES-Iztacala, Universidad Nacional Autónoma de México, Av. De los Barrios 1, Los Reyes Iztacala, Tlalnepantla, Estado de México, 54090, Mexico

Garduño-Javier E.:
 Laboratorio Nacional en Salud FES-Iztacala, Universidad Nacional Autónoma de México, Av. De los Barrios 1, Los Reyes Iztacala, Tlalnepantla, Estado de México, 54090, Mexico

Hernandez-Gomez, Victoria:
 Laboratorio Nacional en Salud FES-Iztacala, Universidad Nacional Autónoma de México, Av. De los Barrios 1, Los Reyes Iztacala, Tlalnepantla, Estado de México, 54090, Mexico

Vaca-Paniagua, Felipe:
 Laboratorio Nacional en Salud FES-Iztacala, Universidad Nacional Autónoma de México, Av. De los Barrios 1, Los Reyes Iztacala, Tlalnepantla, Estado de México, 54090, Mexico

 Unidad de Biomedicina, Facultad de Estudios Superiores (FES)-Iztacala, Universidad Nacional Autónoma de México, Av. De los Barrios 1, Los Reyes Iztacala, Tlalnepantla, Estado de México, 54090, Mexico

Rodriguez-Sosa, Miriam:
 Laboratorio Nacional en Salud FES-Iztacala, Universidad Nacional Autónoma de México, Av. De los Barrios 1, Los Reyes Iztacala, Tlalnepantla, Estado de México, 54090, Mexico

Terrazas, Luis I.:
 Laboratorio Nacional en Salud FES-Iztacala, Universidad Nacional Autónoma de México, Av. De los Barrios 1, Los Reyes Iztacala, Tlalnepantla, Estado de México, 54090, Mexico

 Unidad de Biomedicina, Facultad de Estudios Superiores (FES)-Iztacala, Universidad Nacional Autónoma de México, Av. De los Barrios 1, Los Reyes Iztacala, Tlalnepantla, Estado de México, 54090, Mexico
ISSN: 16616596





INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Editorial
MDPI AG, POSTFACH, CH-4005 BASEL, SWITZERLAND, Suiza
Tipo de documento: Article
Volumen: 22 Número: 20
Páginas:
WOS Id: 000713986500001
ID de PubMed: 34681866
imagen gold, Green Published, Gold