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
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