NLRP3 Inflammasome: A Possible Link Between Obesity-Associated Low-Grade Chronic Inflammation and Colorectal Cancer Development

Emerging evidence reveals that adipose tissue-associated inflammation is a main mechanism whereby obesity promotes colorectal cancer risk and progression. Increased inflammasome activity in adipose tissue has been proposed as an important mediator of obesity-induced inflammation and insulin resistan...

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Main Authors: Patricia Ahechu, Gabriel Zozaya, Pablo Martí, José Luis Hernández-Lizoáin, Jorge Baixauli, Xabier Unamuno, Gema Frühbeck, Victoria Catalán
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-12-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2018.02918/full
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author Patricia Ahechu
Gabriel Zozaya
Pablo Martí
José Luis Hernández-Lizoáin
Jorge Baixauli
Xabier Unamuno
Xabier Unamuno
Gema Frühbeck
Gema Frühbeck
Gema Frühbeck
Gema Frühbeck
Victoria Catalán
Victoria Catalán
Victoria Catalán
author_facet Patricia Ahechu
Gabriel Zozaya
Pablo Martí
José Luis Hernández-Lizoáin
Jorge Baixauli
Xabier Unamuno
Xabier Unamuno
Gema Frühbeck
Gema Frühbeck
Gema Frühbeck
Gema Frühbeck
Victoria Catalán
Victoria Catalán
Victoria Catalán
author_sort Patricia Ahechu
collection DOAJ
description Emerging evidence reveals that adipose tissue-associated inflammation is a main mechanism whereby obesity promotes colorectal cancer risk and progression. Increased inflammasome activity in adipose tissue has been proposed as an important mediator of obesity-induced inflammation and insulin resistance development. Chronic inflammation in tumor microenvironments has a great impact on tumor development and immunity, representing a key factor in the response to therapy. In this context, the inflammasomes, main components of the innate immune system, play an important role in cancer development showing tumor promoting or tumor suppressive actions depending on the type of tumor, the specific inflammasome involved, and the downstream effector molecules. The inflammasomes are large multiprotein complexes with the capacity to regulate the activation of caspase-1. In turn, caspase-1 enhances the proteolytic cleavage and the secretion of the inflammatory cytokines interleukin (IL)-1β and IL-18, leading to infiltration of more immune cells and resulting in the generation and maintenance of an inflammatory microenvironment surrounding cancer cells. The inflammasomes also regulate pyroptosis, a rapid and inflammation-associated form of cell death. Recent studies indicate that the inflammasomes can be activated by fatty acids and high glucose levels linking metabolic danger signals to the activation of inflammation and cancer development. These data suggest that activation of the inflammasomes may represent a crucial step in the obesity-associated cancer development. This review will also focus on the potential of inflammasome-activated pathways to develop new therapeutic strategies for the prevention and treatment of obesity-associated colorectal cancer development.
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spelling doaj.art-7242531d0cd149c39c1c3d2ef37d747b2022-12-22T01:16:40ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-12-01910.3389/fimmu.2018.02918422310NLRP3 Inflammasome: A Possible Link Between Obesity-Associated Low-Grade Chronic Inflammation and Colorectal Cancer DevelopmentPatricia Ahechu0Gabriel Zozaya1Pablo Martí2José Luis Hernández-Lizoáin3Jorge Baixauli4Xabier Unamuno5Xabier Unamuno6Gema Frühbeck7Gema Frühbeck8Gema Frühbeck9Gema Frühbeck10Victoria Catalán11Victoria Catalán12Victoria Catalán13Department of Surgery, Clínica Universidad de Navarra, Pamplona, SpainDepartment of Surgery, Clínica Universidad de Navarra, Pamplona, SpainDepartment of Surgery, Clínica Universidad de Navarra, Pamplona, SpainDepartment of Surgery, Clínica Universidad de Navarra, Pamplona, SpainDepartment of Surgery, Clínica Universidad de Navarra, Pamplona, SpainMetabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, SpainCIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Pamplona, SpainMetabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, SpainCIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Pamplona, SpainObesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra, Pamplona, SpainDepartment of Endocrinology & Nutrition, Clínica Universidad de Navarra, Pamplona, SpainMetabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, SpainCIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Pamplona, SpainObesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra, Pamplona, SpainEmerging evidence reveals that adipose tissue-associated inflammation is a main mechanism whereby obesity promotes colorectal cancer risk and progression. Increased inflammasome activity in adipose tissue has been proposed as an important mediator of obesity-induced inflammation and insulin resistance development. Chronic inflammation in tumor microenvironments has a great impact on tumor development and immunity, representing a key factor in the response to therapy. In this context, the inflammasomes, main components of the innate immune system, play an important role in cancer development showing tumor promoting or tumor suppressive actions depending on the type of tumor, the specific inflammasome involved, and the downstream effector molecules. The inflammasomes are large multiprotein complexes with the capacity to regulate the activation of caspase-1. In turn, caspase-1 enhances the proteolytic cleavage and the secretion of the inflammatory cytokines interleukin (IL)-1β and IL-18, leading to infiltration of more immune cells and resulting in the generation and maintenance of an inflammatory microenvironment surrounding cancer cells. The inflammasomes also regulate pyroptosis, a rapid and inflammation-associated form of cell death. Recent studies indicate that the inflammasomes can be activated by fatty acids and high glucose levels linking metabolic danger signals to the activation of inflammation and cancer development. These data suggest that activation of the inflammasomes may represent a crucial step in the obesity-associated cancer development. This review will also focus on the potential of inflammasome-activated pathways to develop new therapeutic strategies for the prevention and treatment of obesity-associated colorectal cancer development.https://www.frontiersin.org/article/10.3389/fimmu.2018.02918/fullinflammasomeNLRP3inflammationcolon cancerobesityadipose tissue
spellingShingle Patricia Ahechu
Gabriel Zozaya
Pablo Martí
José Luis Hernández-Lizoáin
Jorge Baixauli
Xabier Unamuno
Xabier Unamuno
Gema Frühbeck
Gema Frühbeck
Gema Frühbeck
Gema Frühbeck
Victoria Catalán
Victoria Catalán
Victoria Catalán
NLRP3 Inflammasome: A Possible Link Between Obesity-Associated Low-Grade Chronic Inflammation and Colorectal Cancer Development
Frontiers in Immunology
inflammasome
NLRP3
inflammation
colon cancer
obesity
adipose tissue
title NLRP3 Inflammasome: A Possible Link Between Obesity-Associated Low-Grade Chronic Inflammation and Colorectal Cancer Development
title_full NLRP3 Inflammasome: A Possible Link Between Obesity-Associated Low-Grade Chronic Inflammation and Colorectal Cancer Development
title_fullStr NLRP3 Inflammasome: A Possible Link Between Obesity-Associated Low-Grade Chronic Inflammation and Colorectal Cancer Development
title_full_unstemmed NLRP3 Inflammasome: A Possible Link Between Obesity-Associated Low-Grade Chronic Inflammation and Colorectal Cancer Development
title_short NLRP3 Inflammasome: A Possible Link Between Obesity-Associated Low-Grade Chronic Inflammation and Colorectal Cancer Development
title_sort nlrp3 inflammasome a possible link between obesity associated low grade chronic inflammation and colorectal cancer development
topic inflammasome
NLRP3
inflammation
colon cancer
obesity
adipose tissue
url https://www.frontiersin.org/article/10.3389/fimmu.2018.02918/full
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