Xiaorong Zhu, Jie Yu, Mingqiang Hua, Ning Xu, Lianjuan Wang, Lingkai Chen, Yanhong Jia, Xueyun Zhao
{"title":"多发性骨髓瘤中 NLRP3 炎症小体激活的功能。","authors":"Xiaorong Zhu, Jie Yu, Mingqiang Hua, Ning Xu, Lianjuan Wang, Lingkai Chen, Yanhong Jia, Xueyun Zhao","doi":"10.1080/16078454.2024.2399367","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>The drug resistance of multiple myeloma (MM) cells is one of the main causes of relapse, refractory and progression of MM.</p><p><strong>Methods: </strong>First, Western blot analysis was used to detect the expression levels of NLRP3, ASC, pro-IL-1β and cleaved IL-1β, and RT-qPCR was used to detect the mRNA expression levels of them. The expression levels of IL-1β and IL-18 in the supernatant were detected by ELISA, and the expression levels of these factors in the activated group and the control group were compared to verify the activation of BMMCs and KM3.</p><p><strong>Result: </strong>1. The protein expression of NLRP3 and cleavd-IL-1β in the BMMCs cells was significantly higher than that of the control group (<i>P </i>< 0.05). The mRNA expression levels of caspase-1 and IL-1β were higher than those of the control group (<i>P </i>= 0.03, <i>P </i>= 0.02). 2. The protein expression levels of NLRP3 and cleaved-IL-1β in the KM3 cells were significantly higher than those of the control group (<i>P </i>< 0.05). The expressions of caspase-1 mRNA(<i>P </i>= 0.016) and IL-1β mRNA(<i>P </i>= 0.037) were significantly increased compared with the control group. 3. The early apoptosis results of BMMCs showed that the apoptosis rate of the LPS+ATP+Dex group was lower than that of the Dex group (<i>P </i>= 0.017). The early apoptosis rate of the LPS+ATP+Dex+Vel group was decreased compared with the Dex+Vel group (<i>P </i>= 0.045). 4. The early apoptosis rate of KM3 in the LPS+ATP+Dex group was lower than that in the Dex group (<i>P </i>= 0.03).</p><p><strong>Conclusion: </strong>1. LPS+ATP can activate NLRP3 inflammasome in multiple myeloma cells. 2. Activation of NLRP3 inflammasome inhibits the early apoptosis of myeloma cells induced by dexamethasone and bortezomib.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":null,"pages":null},"PeriodicalIF":2.0000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Function of NLRP3 inflammasome activation in multiple myeloma.\",\"authors\":\"Xiaorong Zhu, Jie Yu, Mingqiang Hua, Ning Xu, Lianjuan Wang, Lingkai Chen, Yanhong Jia, Xueyun Zhao\",\"doi\":\"10.1080/16078454.2024.2399367\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>The drug resistance of multiple myeloma (MM) cells is one of the main causes of relapse, refractory and progression of MM.</p><p><strong>Methods: </strong>First, Western blot analysis was used to detect the expression levels of NLRP3, ASC, pro-IL-1β and cleaved IL-1β, and RT-qPCR was used to detect the mRNA expression levels of them. The expression levels of IL-1β and IL-18 in the supernatant were detected by ELISA, and the expression levels of these factors in the activated group and the control group were compared to verify the activation of BMMCs and KM3.</p><p><strong>Result: </strong>1. The protein expression of NLRP3 and cleavd-IL-1β in the BMMCs cells was significantly higher than that of the control group (<i>P </i>< 0.05). The mRNA expression levels of caspase-1 and IL-1β were higher than those of the control group (<i>P </i>= 0.03, <i>P </i>= 0.02). 2. The protein expression levels of NLRP3 and cleaved-IL-1β in the KM3 cells were significantly higher than those of the control group (<i>P </i>< 0.05). The expressions of caspase-1 mRNA(<i>P </i>= 0.016) and IL-1β mRNA(<i>P </i>= 0.037) were significantly increased compared with the control group. 3. The early apoptosis results of BMMCs showed that the apoptosis rate of the LPS+ATP+Dex group was lower than that of the Dex group (<i>P </i>= 0.017). The early apoptosis rate of the LPS+ATP+Dex+Vel group was decreased compared with the Dex+Vel group (<i>P </i>= 0.045). 4. The early apoptosis rate of KM3 in the LPS+ATP+Dex group was lower than that in the Dex group (<i>P </i>= 0.03).</p><p><strong>Conclusion: </strong>1. LPS+ATP can activate NLRP3 inflammasome in multiple myeloma cells. 2. Activation of NLRP3 inflammasome inhibits the early apoptosis of myeloma cells induced by dexamethasone and bortezomib.</p>\",\"PeriodicalId\":13161,\"journal\":{\"name\":\"Hematology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hematology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/16078454.2024.2399367\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/9/13 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hematology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/16078454.2024.2399367","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/13 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Function of NLRP3 inflammasome activation in multiple myeloma.
Objective: The drug resistance of multiple myeloma (MM) cells is one of the main causes of relapse, refractory and progression of MM.
Methods: First, Western blot analysis was used to detect the expression levels of NLRP3, ASC, pro-IL-1β and cleaved IL-1β, and RT-qPCR was used to detect the mRNA expression levels of them. The expression levels of IL-1β and IL-18 in the supernatant were detected by ELISA, and the expression levels of these factors in the activated group and the control group were compared to verify the activation of BMMCs and KM3.
Result: 1. The protein expression of NLRP3 and cleavd-IL-1β in the BMMCs cells was significantly higher than that of the control group (P < 0.05). The mRNA expression levels of caspase-1 and IL-1β were higher than those of the control group (P = 0.03, P = 0.02). 2. The protein expression levels of NLRP3 and cleaved-IL-1β in the KM3 cells were significantly higher than those of the control group (P < 0.05). The expressions of caspase-1 mRNA(P = 0.016) and IL-1β mRNA(P = 0.037) were significantly increased compared with the control group. 3. The early apoptosis results of BMMCs showed that the apoptosis rate of the LPS+ATP+Dex group was lower than that of the Dex group (P = 0.017). The early apoptosis rate of the LPS+ATP+Dex+Vel group was decreased compared with the Dex+Vel group (P = 0.045). 4. The early apoptosis rate of KM3 in the LPS+ATP+Dex group was lower than that in the Dex group (P = 0.03).
Conclusion: 1. LPS+ATP can activate NLRP3 inflammasome in multiple myeloma cells. 2. Activation of NLRP3 inflammasome inhibits the early apoptosis of myeloma cells induced by dexamethasone and bortezomib.
期刊介绍：
Hematology is an international journal publishing original and review articles in the field of general hematology, including oncology, pathology, biology, clinical research and epidemiology. Of the fixed sections, annotations are accepted on any general or scientific field: technical annotations covering current laboratory practice in general hematology, blood transfusion and clinical trials, and current clinical practice reviews the consensus driven areas of care and management.
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