NLRP3 Inflammasome Promotes the Progression of Acute Myeloid Leukemia via IL-1β Pathway

NLRP3 inflammasome has been reported to be associated with the pathogenesis of multiple solid tumors. However, the role of NLRP3 inflammasome in acute myeloid leukemia (AML) remains unclear. We showed that NLRP3 inflammasome is over-expressed and highly activated in AML bone marrow leukemia cells, w...

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Autores principales:	Chaoqin Zhong, Ruiqing Wang, Mingqiang Hua, Chen Zhang, Fengjiao Han, Miao Xu, Xinyu Yang, Guosheng Li, Xiang Hu, Tao Sun, Chunyan Ji, Daoxin Ma
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	inflammasome NLRP3 IL-1β acute myeloid leukemia progression Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/94ff9651b85e492a86eb35e053197ac9
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spelling	oai:doaj.org-article:94ff9651b85e492a86eb35e053197ac92021-11-16T09:44:53ZNLRP3 Inflammasome Promotes the Progression of Acute Myeloid Leukemia via IL-1β Pathway1664-322410.3389/fimmu.2021.661939https://doaj.org/article/94ff9651b85e492a86eb35e053197ac92021-06-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.661939/fullhttps://doaj.org/toc/1664-3224NLRP3 inflammasome has been reported to be associated with the pathogenesis of multiple solid tumors. However, the role of NLRP3 inflammasome in acute myeloid leukemia (AML) remains unclear. We showed that NLRP3 inflammasome is over-expressed and highly activated in AML bone marrow leukemia cells, which is correlated with poor prognosis. The activation of NLRP3 inflammasome in AML cells promotes leukemia cells proliferation, inhibits apoptosis and increases resistance to chemotherapy, while inactivation of NLRP3 by caspase-1 or NF-κB inhibitor shows leukemia-suppressing effects. Bayesian networks analysis and cell co-culture tests further suggest that NLRP3 inflammasome acts through IL-1β but not IL-18 in AML. Knocking down endogenous IL-1β or anti-IL-1β antibody inhibits leukemia cells whereas IL-1β cytokine enhances leukemia proliferation. In AML murine model, up-regulation of NLRP3 increases the leukemia burden in bone marrow, spleen and liver, and shortens the survival time; furthermore, knocking out NLRP3 inhibits leukemia progression. Collectively, all these evidences demonstrate that NLRP3 inflammasome promotes AML progression in an IL-1β dependent manner, and targeting NLRP3 inflammasome may provide a novel therapeutic option for AML.Chaoqin ZhongChaoqin ZhongRuiqing WangMingqiang HuaMingqiang HuaChen ZhangFengjiao HanMiao XuXinyu YangGuosheng LiXiang HuTao SunChunyan JiDaoxin MaFrontiers Media S.A.articleinflammasomeNLRP3IL-1βacute myeloid leukemiaprogressionImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	inflammasome NLRP3 IL-1β acute myeloid leukemia progression Immunologic diseases. Allergy RC581-607
spellingShingle	inflammasome NLRP3 IL-1β acute myeloid leukemia progression Immunologic diseases. Allergy RC581-607 Chaoqin Zhong Chaoqin Zhong Ruiqing Wang Mingqiang Hua Mingqiang Hua Chen Zhang Fengjiao Han Miao Xu Xinyu Yang Guosheng Li Xiang Hu Tao Sun Chunyan Ji Daoxin Ma NLRP3 Inflammasome Promotes the Progression of Acute Myeloid Leukemia via IL-1β Pathway
description	NLRP3 inflammasome has been reported to be associated with the pathogenesis of multiple solid tumors. However, the role of NLRP3 inflammasome in acute myeloid leukemia (AML) remains unclear. We showed that NLRP3 inflammasome is over-expressed and highly activated in AML bone marrow leukemia cells, which is correlated with poor prognosis. The activation of NLRP3 inflammasome in AML cells promotes leukemia cells proliferation, inhibits apoptosis and increases resistance to chemotherapy, while inactivation of NLRP3 by caspase-1 or NF-κB inhibitor shows leukemia-suppressing effects. Bayesian networks analysis and cell co-culture tests further suggest that NLRP3 inflammasome acts through IL-1β but not IL-18 in AML. Knocking down endogenous IL-1β or anti-IL-1β antibody inhibits leukemia cells whereas IL-1β cytokine enhances leukemia proliferation. In AML murine model, up-regulation of NLRP3 increases the leukemia burden in bone marrow, spleen and liver, and shortens the survival time; furthermore, knocking out NLRP3 inhibits leukemia progression. Collectively, all these evidences demonstrate that NLRP3 inflammasome promotes AML progression in an IL-1β dependent manner, and targeting NLRP3 inflammasome may provide a novel therapeutic option for AML.
format	article
author	Chaoqin Zhong Chaoqin Zhong Ruiqing Wang Mingqiang Hua Mingqiang Hua Chen Zhang Fengjiao Han Miao Xu Xinyu Yang Guosheng Li Xiang Hu Tao Sun Chunyan Ji Daoxin Ma
author_facet	Chaoqin Zhong Chaoqin Zhong Ruiqing Wang Mingqiang Hua Mingqiang Hua Chen Zhang Fengjiao Han Miao Xu Xinyu Yang Guosheng Li Xiang Hu Tao Sun Chunyan Ji Daoxin Ma
author_sort	Chaoqin Zhong
title	NLRP3 Inflammasome Promotes the Progression of Acute Myeloid Leukemia via IL-1β Pathway
title_short	NLRP3 Inflammasome Promotes the Progression of Acute Myeloid Leukemia via IL-1β Pathway
title_full	NLRP3 Inflammasome Promotes the Progression of Acute Myeloid Leukemia via IL-1β Pathway
title_fullStr	NLRP3 Inflammasome Promotes the Progression of Acute Myeloid Leukemia via IL-1β Pathway
title_full_unstemmed	NLRP3 Inflammasome Promotes the Progression of Acute Myeloid Leukemia via IL-1β Pathway
title_sort	nlrp3 inflammasome promotes the progression of acute myeloid leukemia via il-1β pathway
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/94ff9651b85e492a86eb35e053197ac9
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NLRP3 Inflammasome Promotes the Progression of Acute Myeloid Leukemia via IL-1β Pathway

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