Free immunoglobulin light chain (FLC) promotes murine colitis and colitis-associated colon carcinogenesis by activating the inflammasome

Abstract Numerous studies have demonstrated that free Ig light chain (FLC), a novel inflammation mediator, participates in many inflammatory diseases by activating mast cells and extending the survival of neutrophils. However, it remains unclear whether FLC is involved in colitis and colitis-associa...

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Autores principales:	Junfan Ma, Dongyang Jiang, Xiaoting Gong, Wenwei Shao, Zhu Zhu, Weiyan Xu, Xiaoyan Qiu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/90d113f7ff9b4b56b47fe033a83da7f0
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spelling	oai:doaj.org-article:90d113f7ff9b4b56b47fe033a83da7f02021-12-02T15:04:58ZFree immunoglobulin light chain (FLC) promotes murine colitis and colitis-associated colon carcinogenesis by activating the inflammasome10.1038/s41598-017-05468-w2045-2322https://doaj.org/article/90d113f7ff9b4b56b47fe033a83da7f02017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05468-whttps://doaj.org/toc/2045-2322Abstract Numerous studies have demonstrated that free Ig light chain (FLC), a novel inflammation mediator, participates in many inflammatory diseases by activating mast cells and extending the survival of neutrophils. However, it remains unclear whether FLC is involved in colitis and colitis-associated colon carcinogenesis (CAC). In this study, we found a significant increase in FLC in murine models of DSS (Dextran Sulfate Sodium Salt)-induced colitis and CAC compared to controls. Peptide F991, a functional blocker of FLC, significantly attenuated colitis progression, which included abrogating the development of diarrhea and tumor burden, elevating survival rate, greatly reducing the infiltration of inflammatory cells (such as ROS+ active neutrophils), especially reducing tumorigenesis in CAC. Furthermore, we demonstrated that F991 inhibited the activation of the inflammasome by reducing the expression of cleaved caspase-1 and the maturation of IL-1β and IL-18. Altogether, our findings demonstrate that FLC can promote the pathogenesis of colitis and CAC and may be used as novel biomarker for the diagnosis of inflammatory bowel disease. Additionally, F991 may become a potential therapeutic option for colitis or colorectal cancer.Junfan MaDongyang JiangXiaoting GongWenwei ShaoZhu ZhuWeiyan XuXiaoyan QiuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Junfan Ma Dongyang Jiang Xiaoting Gong Wenwei Shao Zhu Zhu Weiyan Xu Xiaoyan Qiu Free immunoglobulin light chain (FLC) promotes murine colitis and colitis-associated colon carcinogenesis by activating the inflammasome
description	Abstract Numerous studies have demonstrated that free Ig light chain (FLC), a novel inflammation mediator, participates in many inflammatory diseases by activating mast cells and extending the survival of neutrophils. However, it remains unclear whether FLC is involved in colitis and colitis-associated colon carcinogenesis (CAC). In this study, we found a significant increase in FLC in murine models of DSS (Dextran Sulfate Sodium Salt)-induced colitis and CAC compared to controls. Peptide F991, a functional blocker of FLC, significantly attenuated colitis progression, which included abrogating the development of diarrhea and tumor burden, elevating survival rate, greatly reducing the infiltration of inflammatory cells (such as ROS+ active neutrophils), especially reducing tumorigenesis in CAC. Furthermore, we demonstrated that F991 inhibited the activation of the inflammasome by reducing the expression of cleaved caspase-1 and the maturation of IL-1β and IL-18. Altogether, our findings demonstrate that FLC can promote the pathogenesis of colitis and CAC and may be used as novel biomarker for the diagnosis of inflammatory bowel disease. Additionally, F991 may become a potential therapeutic option for colitis or colorectal cancer.
format	article
author	Junfan Ma Dongyang Jiang Xiaoting Gong Wenwei Shao Zhu Zhu Weiyan Xu Xiaoyan Qiu
author_facet	Junfan Ma Dongyang Jiang Xiaoting Gong Wenwei Shao Zhu Zhu Weiyan Xu Xiaoyan Qiu
author_sort	Junfan Ma
title	Free immunoglobulin light chain (FLC) promotes murine colitis and colitis-associated colon carcinogenesis by activating the inflammasome
title_short	Free immunoglobulin light chain (FLC) promotes murine colitis and colitis-associated colon carcinogenesis by activating the inflammasome
title_full	Free immunoglobulin light chain (FLC) promotes murine colitis and colitis-associated colon carcinogenesis by activating the inflammasome
title_fullStr	Free immunoglobulin light chain (FLC) promotes murine colitis and colitis-associated colon carcinogenesis by activating the inflammasome
title_full_unstemmed	Free immunoglobulin light chain (FLC) promotes murine colitis and colitis-associated colon carcinogenesis by activating the inflammasome
title_sort	free immunoglobulin light chain (flc) promotes murine colitis and colitis-associated colon carcinogenesis by activating the inflammasome
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/90d113f7ff9b4b56b47fe033a83da7f0
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Free immunoglobulin light chain (FLC) promotes murine colitis and colitis-associated colon carcinogenesis by activating the inflammasome

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