p21-Activated Kinase 4 Signaling Promotes Japanese Encephalitis Virus-Mediated Inflammation in Astrocytes
Japanese encephalitis virus (JEV) targets central nervous system, resulting in neuroinflammation with typical features of neuronal death along with hyper activation of glial cells. Exploring the mechanisms responsible for the JEV-caused inflammatory response remains a pivotal area of research. In th...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-06-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fcimb.2017.00271/full |
| _version_ | 1819075859529596928 |
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| author | Wen He Wen He Wen He Zikai Zhao Zikai Zhao Zikai Zhao Awais Anees Awais Anees Awais Anees Yunchuan Li Yunchuan Li Yunchuan Li Usama Ashraf Usama Ashraf Usama Ashraf Zheng Chen Zheng Chen Zheng Chen Yunfeng Song Yunfeng Song Yunfeng Song Huanchun Chen Huanchun Chen Huanchun Chen Shengbo Cao Shengbo Cao Shengbo Cao Jing Ye Jing Ye Jing Ye Jing Ye |
| author_facet | Wen He Wen He Wen He Zikai Zhao Zikai Zhao Zikai Zhao Awais Anees Awais Anees Awais Anees Yunchuan Li Yunchuan Li Yunchuan Li Usama Ashraf Usama Ashraf Usama Ashraf Zheng Chen Zheng Chen Zheng Chen Yunfeng Song Yunfeng Song Yunfeng Song Huanchun Chen Huanchun Chen Huanchun Chen Shengbo Cao Shengbo Cao Shengbo Cao Jing Ye Jing Ye Jing Ye Jing Ye |
| author_sort | Wen He |
| collection | DOAJ |
| description | Japanese encephalitis virus (JEV) targets central nervous system, resulting in neuroinflammation with typical features of neuronal death along with hyper activation of glial cells. Exploring the mechanisms responsible for the JEV-caused inflammatory response remains a pivotal area of research. In the present study, we have explored the function of p21-activated kinase 4 (PAK4) in JEV-mediated inflammatory response in human astrocytes. The results showed that JEV infection enhances the phosphorylation of PAK4 in U251 cells and mouse brain. Knockdown of PAK4 resulted in decreased expression of inflammatory cytokines that include tumor necrosis factor alpha, interleukin-6, interleukin-1β, and chemokine (C-C motif) ligand 5 and interferon β upon JEV infection, suggesting that PAK4 signaling promotes JEV-mediated inflammation. In addition, we found that knockdown of PAK4 led to the inhibition of MAPK signaling including ERK, p38 MAPK and JNK, and also resulted in the reduced nuclear translocation of NF-κB and phosphorylation of AP-1. These results demonstrate that PAK4 signaling actively promotes JEV-mediated inflammation in human astrocytes via MAPK-NF-κB/AP-1 pathway, which will provide a new insight into the molecular mechanism of the JEV-induced inflammatory response. |
| first_indexed | 2024-12-21T18:32:06Z |
| format | Article |
| id | doaj.art-dc6aa16978e740bebe93964a0fa7166a |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-21T18:32:06Z |
| publishDate | 2017-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-dc6aa16978e740bebe93964a0fa7166a2022-12-21T18:54:15ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882017-06-01710.3389/fcimb.2017.00271255641p21-Activated Kinase 4 Signaling Promotes Japanese Encephalitis Virus-Mediated Inflammation in AstrocytesWen He0Wen He1Wen He2Zikai Zhao3Zikai Zhao4Zikai Zhao5Awais Anees6Awais Anees7Awais Anees8Yunchuan Li9Yunchuan Li10Yunchuan Li11Usama Ashraf12Usama Ashraf13Usama Ashraf14Zheng Chen15Zheng Chen16Zheng Chen17Yunfeng Song18Yunfeng Song19Yunfeng Song20Huanchun Chen21Huanchun Chen22Huanchun Chen23Shengbo Cao24Shengbo Cao25Shengbo Cao26Jing Ye27Jing Ye28Jing Ye29Jing Ye30State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural UniversityWuhan, ChinaLaboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural UniversityWuhan, ChinaThe Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural UniversityWuhan, ChinaState Key Laboratory of Agricultural Microbiology, Huazhong Agricultural UniversityWuhan, ChinaLaboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural UniversityWuhan, ChinaThe Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural UniversityWuhan, ChinaState Key Laboratory of Agricultural Microbiology, Huazhong Agricultural UniversityWuhan, ChinaLaboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural UniversityWuhan, ChinaThe Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural UniversityWuhan, ChinaState Key Laboratory of Agricultural Microbiology, Huazhong Agricultural UniversityWuhan, ChinaLaboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural UniversityWuhan, ChinaThe Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural UniversityWuhan, ChinaState Key Laboratory of Agricultural Microbiology, Huazhong Agricultural UniversityWuhan, ChinaLaboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural UniversityWuhan, ChinaThe Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural UniversityWuhan, ChinaState Key Laboratory of Agricultural Microbiology, Huazhong Agricultural UniversityWuhan, ChinaLaboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural UniversityWuhan, ChinaThe Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural UniversityWuhan, ChinaState Key Laboratory of Agricultural Microbiology, Huazhong Agricultural UniversityWuhan, ChinaLaboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural UniversityWuhan, ChinaThe Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural UniversityWuhan, ChinaState Key Laboratory of Agricultural Microbiology, Huazhong Agricultural UniversityWuhan, ChinaLaboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural UniversityWuhan, ChinaThe Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural UniversityWuhan, ChinaState Key Laboratory of Agricultural Microbiology, Huazhong Agricultural UniversityWuhan, ChinaLaboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural UniversityWuhan, ChinaThe Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural UniversityWuhan, ChinaState Key Laboratory of Agricultural Microbiology, Huazhong Agricultural UniversityWuhan, ChinaLaboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural UniversityWuhan, ChinaThe Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural UniversityWuhan, ChinaCollege of Life Science and Technology, Huazhong Agricultural UniversityWuhan, ChinaJapanese encephalitis virus (JEV) targets central nervous system, resulting in neuroinflammation with typical features of neuronal death along with hyper activation of glial cells. Exploring the mechanisms responsible for the JEV-caused inflammatory response remains a pivotal area of research. In the present study, we have explored the function of p21-activated kinase 4 (PAK4) in JEV-mediated inflammatory response in human astrocytes. The results showed that JEV infection enhances the phosphorylation of PAK4 in U251 cells and mouse brain. Knockdown of PAK4 resulted in decreased expression of inflammatory cytokines that include tumor necrosis factor alpha, interleukin-6, interleukin-1β, and chemokine (C-C motif) ligand 5 and interferon β upon JEV infection, suggesting that PAK4 signaling promotes JEV-mediated inflammation. In addition, we found that knockdown of PAK4 led to the inhibition of MAPK signaling including ERK, p38 MAPK and JNK, and also resulted in the reduced nuclear translocation of NF-κB and phosphorylation of AP-1. These results demonstrate that PAK4 signaling actively promotes JEV-mediated inflammation in human astrocytes via MAPK-NF-κB/AP-1 pathway, which will provide a new insight into the molecular mechanism of the JEV-induced inflammatory response.http://journal.frontiersin.org/article/10.3389/fcimb.2017.00271/fullJEVPAK4inflammationMAPKastrocyte |
| spellingShingle | Wen He Wen He Wen He Zikai Zhao Zikai Zhao Zikai Zhao Awais Anees Awais Anees Awais Anees Yunchuan Li Yunchuan Li Yunchuan Li Usama Ashraf Usama Ashraf Usama Ashraf Zheng Chen Zheng Chen Zheng Chen Yunfeng Song Yunfeng Song Yunfeng Song Huanchun Chen Huanchun Chen Huanchun Chen Shengbo Cao Shengbo Cao Shengbo Cao Jing Ye Jing Ye Jing Ye Jing Ye p21-Activated Kinase 4 Signaling Promotes Japanese Encephalitis Virus-Mediated Inflammation in Astrocytes Frontiers in Cellular and Infection Microbiology JEV PAK4 inflammation MAPK astrocyte |
| title | p21-Activated Kinase 4 Signaling Promotes Japanese Encephalitis Virus-Mediated Inflammation in Astrocytes |
| title_full | p21-Activated Kinase 4 Signaling Promotes Japanese Encephalitis Virus-Mediated Inflammation in Astrocytes |
| title_fullStr | p21-Activated Kinase 4 Signaling Promotes Japanese Encephalitis Virus-Mediated Inflammation in Astrocytes |
| title_full_unstemmed | p21-Activated Kinase 4 Signaling Promotes Japanese Encephalitis Virus-Mediated Inflammation in Astrocytes |
| title_short | p21-Activated Kinase 4 Signaling Promotes Japanese Encephalitis Virus-Mediated Inflammation in Astrocytes |
| title_sort | p21 activated kinase 4 signaling promotes japanese encephalitis virus mediated inflammation in astrocytes |
| topic | JEV PAK4 inflammation MAPK astrocyte |
| url | http://journal.frontiersin.org/article/10.3389/fcimb.2017.00271/full |
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