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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.661939/full |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T00:03:00Z |
| format | Article |
| id | doaj.art-94ff9651b85e492a86eb35e053197ac9 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T00:03:00Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-94ff9651b85e492a86eb35e053197ac92022-12-21T20:46:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-06-011210.3389/fimmu.2021.661939661939NLRP3 Inflammasome Promotes the Progression of Acute Myeloid Leukemia via IL-1β PathwayChaoqin Zhong0Chaoqin Zhong1Ruiqing Wang2Mingqiang Hua3Mingqiang Hua4Chen Zhang5Fengjiao Han6Miao Xu7Xinyu Yang8Guosheng Li9Xiang Hu10Tao Sun11Chunyan Ji12Daoxin Ma13Department of Hematology, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Hematology, Shandong Yantai Mountain Hospital, Yantai, ChinaDepartment of Hematology, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Hematology, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Emergency, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Hematology, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Hematology, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Hematology, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Hematology, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Hematology, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Hematology, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Hematology, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Hematology, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Hematology, Qilu Hospital of Shandong University, Jinan, ChinaNLRP3 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.661939/fullinflammasomeNLRP3IL-1βacute myeloid leukemiaprogression |
| spellingShingle | 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 Frontiers in Immunology inflammasome NLRP3 IL-1β acute myeloid leukemia progression |
| title | 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_short | 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 |
| topic | inflammasome NLRP3 IL-1β acute myeloid leukemia progression |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.661939/full |
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