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MK2: an unrecognized regulator of tumor promoting macrophages in colorectal cancer?

Colorectal cancer (CRC) is one of the most common malignancies and is associated closely with inflammation before and after development. Macrophages promote colitis and colitis-associated CRC. M1 macrophages contribute to colitis directly through the production of proinflammatory cytokines and throu...

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Autores principales: Castillo, Eliseo F., Ray, Anita L., Beswick, Ellen J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4798244/
https://www.ncbi.nlm.nih.gov/pubmed/26998523
http://dx.doi.org/10.14800/macrophage.1166
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author Castillo, Eliseo F.
Ray, Anita L.
Beswick, Ellen J.
author_facet Castillo, Eliseo F.
Ray, Anita L.
Beswick, Ellen J.
author_sort Castillo, Eliseo F.
collection PubMed
description Colorectal cancer (CRC) is one of the most common malignancies and is associated closely with inflammation before and after development. Macrophages promote colitis and colitis-associated CRC. M1 macrophages contribute to colitis directly through the production of proinflammatory cytokines and through activation of proinflammatory immune cell phenotypes. In cancer, both M1 and M2 macrophages participate in tumor development and progression through cytokine production, changes in cell signaling and activation of T cells. We have identified the mitogen-activated protein kinase-activated protein kinase 2 (MK2) as a regulator of macrophages during colitis-associated CRC (CAC). MK2 is a proinflammatory kinase that promotes production of IL-1α, IL-1β, IL-6 and TNF-α. MK2(−/−) mice have decreases in macrophages, macrophage-associated chemokines, and proinflammatory cytokines. Most significantly, MK2(−/−) mice do not develop neoplasms in an inflammatory model of CRC. However, addition of MK2(+/+) macrophages to MK2(−/−) mice increases production of proinflammatory cytokines. In wild type mice, both cytokines and tumor burdens increase upon addition of additional macrophages. These data support the importance of MK2 in macrophage regulation during inflammation-associated CRC.
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spelling pubmed-47982442016-03-18 MK2: an unrecognized regulator of tumor promoting macrophages in colorectal cancer? Castillo, Eliseo F. Ray, Anita L. Beswick, Ellen J. Macrophage (Houst) Article Colorectal cancer (CRC) is one of the most common malignancies and is associated closely with inflammation before and after development. Macrophages promote colitis and colitis-associated CRC. M1 macrophages contribute to colitis directly through the production of proinflammatory cytokines and through activation of proinflammatory immune cell phenotypes. In cancer, both M1 and M2 macrophages participate in tumor development and progression through cytokine production, changes in cell signaling and activation of T cells. We have identified the mitogen-activated protein kinase-activated protein kinase 2 (MK2) as a regulator of macrophages during colitis-associated CRC (CAC). MK2 is a proinflammatory kinase that promotes production of IL-1α, IL-1β, IL-6 and TNF-α. MK2(−/−) mice have decreases in macrophages, macrophage-associated chemokines, and proinflammatory cytokines. Most significantly, MK2(−/−) mice do not develop neoplasms in an inflammatory model of CRC. However, addition of MK2(+/+) macrophages to MK2(−/−) mice increases production of proinflammatory cytokines. In wild type mice, both cytokines and tumor burdens increase upon addition of additional macrophages. These data support the importance of MK2 in macrophage regulation during inflammation-associated CRC. 2016-02-01 2016 /pmc/articles/PMC4798244/ /pubmed/26998523 http://dx.doi.org/10.14800/macrophage.1166 Text en http://creativecommons.org/licenses/by/4.0/ Licensed under a Creative Commons Attribution 4.0 International License which allows users including authors of articles to copy and redistribute the material in any medium or format, in addition to remix, transform, and build upon the material for any purpose, even commercially, as long as the author and original source are properly cited or credited.
spellingShingle Article
Castillo, Eliseo F.
Ray, Anita L.
Beswick, Ellen J.
MK2: an unrecognized regulator of tumor promoting macrophages in colorectal cancer?
title MK2: an unrecognized regulator of tumor promoting macrophages in colorectal cancer?
title_full MK2: an unrecognized regulator of tumor promoting macrophages in colorectal cancer?
title_fullStr MK2: an unrecognized regulator of tumor promoting macrophages in colorectal cancer?
title_full_unstemmed MK2: an unrecognized regulator of tumor promoting macrophages in colorectal cancer?
title_short MK2: an unrecognized regulator of tumor promoting macrophages in colorectal cancer?
title_sort mk2: an unrecognized regulator of tumor promoting macrophages in colorectal cancer?
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4798244/
https://www.ncbi.nlm.nih.gov/pubmed/26998523
http://dx.doi.org/10.14800/macrophage.1166
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