Epithelial-derived IL-33 promotes intestinal tumorigenesis in Apc Min/+ mice

Abstract Increased expression of Interleukin (IL)-33 has been detected in intestinal samples of patients with ulcerative colitis, a condition associated with increased risk for colon cancer, but its role in the development of colorectal cancer has yet to be fully examined. Here, we investigated the...

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Autores principales:	Zhengxiang He, Lili Chen, Fabricio O. Souto, Claudia Canasto-Chibuque, Gerold Bongers, Madhura Deshpande, Noam Harpaz, Huaibin M. Ko, Kevin Kelley, Glaucia C. Furtado, Sergio A. Lira
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/88385b01bc9042b29b43f9645a0ed849
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spelling	oai:doaj.org-article:88385b01bc9042b29b43f9645a0ed8492021-12-02T16:06:39ZEpithelial-derived IL-33 promotes intestinal tumorigenesis in Apc Min/+ mice10.1038/s41598-017-05716-z2045-2322https://doaj.org/article/88385b01bc9042b29b43f9645a0ed8492017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05716-zhttps://doaj.org/toc/2045-2322Abstract Increased expression of Interleukin (IL)-33 has been detected in intestinal samples of patients with ulcerative colitis, a condition associated with increased risk for colon cancer, but its role in the development of colorectal cancer has yet to be fully examined. Here, we investigated the role of epithelial expressed IL-33 during development of intestinal tumors. IL-33 expression was detected in epithelial cells in colorectal cancer specimens and in the Apc Min/+ mice. To better understand the role of epithelial-derived IL-33 in the intestinal tumorigenesis, we generated transgenic mice expressing IL-33 in intestinal epithelial cells (V33 mice). V33 Apc Min/+ mice, resulting from the cross of V33 with Apc Min/+ mice, had increased intestinal tumor burden compared with littermate Apc Min/+ mice. Consistently, Apc Min/+ mice deficient for IL-33 receptor (ST2), had reduced polyp burden. Mechanistically, overexpression of IL-33 promoted expansion of ST2+ regulatory T cells, increased Th2 cytokine milieu, and induced alternatively activated macrophages in the gut. IL-33 promoted marked changes in the expression of antimicrobial peptides, and antibiotic treatment of V33 Apc Min/+ mice abrogated the tumor promoting-effects of IL-33 in the colon. In conclusion, elevated IL-33 signaling increases tumor development in the Apc Min/+ mice.Zhengxiang HeLili ChenFabricio O. SoutoClaudia Canasto-ChibuqueGerold BongersMadhura DeshpandeNoam HarpazHuaibin M. KoKevin KelleyGlaucia C. FurtadoSergio A. LiraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zhengxiang He Lili Chen Fabricio O. Souto Claudia Canasto-Chibuque Gerold Bongers Madhura Deshpande Noam Harpaz Huaibin M. Ko Kevin Kelley Glaucia C. Furtado Sergio A. Lira Epithelial-derived IL-33 promotes intestinal tumorigenesis in Apc Min/+ mice
description	Abstract Increased expression of Interleukin (IL)-33 has been detected in intestinal samples of patients with ulcerative colitis, a condition associated with increased risk for colon cancer, but its role in the development of colorectal cancer has yet to be fully examined. Here, we investigated the role of epithelial expressed IL-33 during development of intestinal tumors. IL-33 expression was detected in epithelial cells in colorectal cancer specimens and in the Apc Min/+ mice. To better understand the role of epithelial-derived IL-33 in the intestinal tumorigenesis, we generated transgenic mice expressing IL-33 in intestinal epithelial cells (V33 mice). V33 Apc Min/+ mice, resulting from the cross of V33 with Apc Min/+ mice, had increased intestinal tumor burden compared with littermate Apc Min/+ mice. Consistently, Apc Min/+ mice deficient for IL-33 receptor (ST2), had reduced polyp burden. Mechanistically, overexpression of IL-33 promoted expansion of ST2+ regulatory T cells, increased Th2 cytokine milieu, and induced alternatively activated macrophages in the gut. IL-33 promoted marked changes in the expression of antimicrobial peptides, and antibiotic treatment of V33 Apc Min/+ mice abrogated the tumor promoting-effects of IL-33 in the colon. In conclusion, elevated IL-33 signaling increases tumor development in the Apc Min/+ mice.
format	article
author	Zhengxiang He Lili Chen Fabricio O. Souto Claudia Canasto-Chibuque Gerold Bongers Madhura Deshpande Noam Harpaz Huaibin M. Ko Kevin Kelley Glaucia C. Furtado Sergio A. Lira
author_facet	Zhengxiang He Lili Chen Fabricio O. Souto Claudia Canasto-Chibuque Gerold Bongers Madhura Deshpande Noam Harpaz Huaibin M. Ko Kevin Kelley Glaucia C. Furtado Sergio A. Lira
author_sort	Zhengxiang He
title	Epithelial-derived IL-33 promotes intestinal tumorigenesis in Apc Min/+ mice
title_short	Epithelial-derived IL-33 promotes intestinal tumorigenesis in Apc Min/+ mice
title_full	Epithelial-derived IL-33 promotes intestinal tumorigenesis in Apc Min/+ mice
title_fullStr	Epithelial-derived IL-33 promotes intestinal tumorigenesis in Apc Min/+ mice
title_full_unstemmed	Epithelial-derived IL-33 promotes intestinal tumorigenesis in Apc Min/+ mice
title_sort	epithelial-derived il-33 promotes intestinal tumorigenesis in apc min/+ mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/88385b01bc9042b29b43f9645a0ed849
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Epithelial-derived IL-33 promotes intestinal tumorigenesis in Apc Min/+ mice

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