Phosphorylation of ERK-Dependent NF-κB Triggers NLRP3 Inflammasome Mediated by Vimentin in EV71-Infected Glioblastoma Cells
Enterovirus 71 (EV71) is a dominant pathogenic agent that may cause severe central nervous system (CNS) diseases among infants and young children in the Asia-pacific. The inflammasome is closely implicated in EV71-induced CNS injuries through a series of signaling pathways. However, the activation p...
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MDPI AG
2022-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/13/4190 |
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| author | Zelong Gong Xuefeng Gao Qingqing Yang Jingxian Lun Hansen Xiao Jiayu Zhong Hong Cao |
| author_facet | Zelong Gong Xuefeng Gao Qingqing Yang Jingxian Lun Hansen Xiao Jiayu Zhong Hong Cao |
| author_sort | Zelong Gong |
| collection | DOAJ |
| description | Enterovirus 71 (EV71) is a dominant pathogenic agent that may cause severe central nervous system (CNS) diseases among infants and young children in the Asia-pacific. The inflammasome is closely implicated in EV71-induced CNS injuries through a series of signaling pathways. However, the activation pathway of NLRP3 inflammasome involved in EV71-mediated CNS injuries remains poorly defined. In the studies, EV71 infection, ERK1/2 phosphorylation, and activation of NLRP3 are abolished in glioblastoma cells with low vimentin expression by CRISPR/Cas9-mediated knockdown. PD098059, an inhibitor of p-ERK, remarkably blocks the vimentin-mediated ERK1/2 phosphorylation in EV71-infected cells. Nuclear translocation of NF-κB p65 is dependent on p-ERK in a time-dependent manner. Moreover, NLRP3 activation and caspase-1 production are limited in EV71-infected cells upon the caffeic acid phenethyl ester (CAPE) administration, an inhibitor of NF-κB, which contributes to the inflammasome regulation. In conclusion, these results suggest that EV71-mediated NLRP3 inflammasome could be activated via the VIM-ERK-NF-κB pathway, and the treatment of the dephosphorylation of ERK and NF-κB inhibitors is beneficial to host defense in EV71-infected CNS. |
| first_indexed | 2024-03-09T04:00:46Z |
| format | Article |
| id | doaj.art-bfeb247ea69c42eb998e328aca794db8 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T04:00:46Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-bfeb247ea69c42eb998e328aca794db82023-12-03T14:13:43ZengMDPI AGMolecules1420-30492022-06-012713419010.3390/molecules27134190Phosphorylation of ERK-Dependent NF-κB Triggers NLRP3 Inflammasome Mediated by Vimentin in EV71-Infected Glioblastoma CellsZelong Gong0Xuefeng Gao1Qingqing Yang2Jingxian Lun3Hansen Xiao4Jiayu Zhong5Hong Cao6Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaGuangdong Provincial Key Laboratory of Tropical Disease Research, Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaGuangdong Provincial Key Laboratory of Tropical Disease Research, Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaGuangdong Provincial Key Laboratory of Tropical Disease Research, Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaGuangdong Provincial Key Laboratory of Tropical Disease Research, Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaGuangdong Provincial Key Laboratory of Tropical Disease Research, Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaGuangdong Provincial Key Laboratory of Tropical Disease Research, Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaEnterovirus 71 (EV71) is a dominant pathogenic agent that may cause severe central nervous system (CNS) diseases among infants and young children in the Asia-pacific. The inflammasome is closely implicated in EV71-induced CNS injuries through a series of signaling pathways. However, the activation pathway of NLRP3 inflammasome involved in EV71-mediated CNS injuries remains poorly defined. In the studies, EV71 infection, ERK1/2 phosphorylation, and activation of NLRP3 are abolished in glioblastoma cells with low vimentin expression by CRISPR/Cas9-mediated knockdown. PD098059, an inhibitor of p-ERK, remarkably blocks the vimentin-mediated ERK1/2 phosphorylation in EV71-infected cells. Nuclear translocation of NF-κB p65 is dependent on p-ERK in a time-dependent manner. Moreover, NLRP3 activation and caspase-1 production are limited in EV71-infected cells upon the caffeic acid phenethyl ester (CAPE) administration, an inhibitor of NF-κB, which contributes to the inflammasome regulation. In conclusion, these results suggest that EV71-mediated NLRP3 inflammasome could be activated via the VIM-ERK-NF-κB pathway, and the treatment of the dephosphorylation of ERK and NF-κB inhibitors is beneficial to host defense in EV71-infected CNS.https://www.mdpi.com/1420-3049/27/13/4190enterovirus 71phosphorylation of ERK1/2NLRP3vimentinNF-κBglioblastoma cells |
| spellingShingle | Zelong Gong Xuefeng Gao Qingqing Yang Jingxian Lun Hansen Xiao Jiayu Zhong Hong Cao Phosphorylation of ERK-Dependent NF-κB Triggers NLRP3 Inflammasome Mediated by Vimentin in EV71-Infected Glioblastoma Cells Molecules enterovirus 71 phosphorylation of ERK1/2 NLRP3 vimentin NF-κB glioblastoma cells |
| title | Phosphorylation of ERK-Dependent NF-κB Triggers NLRP3 Inflammasome Mediated by Vimentin in EV71-Infected Glioblastoma Cells |
| title_full | Phosphorylation of ERK-Dependent NF-κB Triggers NLRP3 Inflammasome Mediated by Vimentin in EV71-Infected Glioblastoma Cells |
| title_fullStr | Phosphorylation of ERK-Dependent NF-κB Triggers NLRP3 Inflammasome Mediated by Vimentin in EV71-Infected Glioblastoma Cells |
| title_full_unstemmed | Phosphorylation of ERK-Dependent NF-κB Triggers NLRP3 Inflammasome Mediated by Vimentin in EV71-Infected Glioblastoma Cells |
| title_short | Phosphorylation of ERK-Dependent NF-κB Triggers NLRP3 Inflammasome Mediated by Vimentin in EV71-Infected Glioblastoma Cells |
| title_sort | phosphorylation of erk dependent nf κb triggers nlrp3 inflammasome mediated by vimentin in ev71 infected glioblastoma cells |
| topic | enterovirus 71 phosphorylation of ERK1/2 NLRP3 vimentin NF-κB glioblastoma cells |
| url | https://www.mdpi.com/1420-3049/27/13/4190 |
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