Curcumin-dependent phenotypic transformation of microglia mediates resistance to pseudorabies-induced encephalitis
Abstract Pseudorabies virus (PRV) causes viral encephalitis, a devastating disease with high mortality worldwide. Curcumin (CUR) can reduce inflammatory damage by altering the phenotype of microglia; however, whether and how these changes mediate resistance to PRV-induced encephalitis is still uncle...
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| Language: | English |
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BMC
2023-03-01
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| Series: | Veterinary Research |
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| Online Access: | https://doi.org/10.1186/s13567-023-01149-x |
| _version_ | 1797863828710490112 |
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| author | Luqiu Feng Guodong Luo Yuhang Li Chen Zhang Yuxuan Liu Yanqing Liu Hongyue Chen Daoling He Yan Zhu Ling Gan |
| author_facet | Luqiu Feng Guodong Luo Yuhang Li Chen Zhang Yuxuan Liu Yanqing Liu Hongyue Chen Daoling He Yan Zhu Ling Gan |
| author_sort | Luqiu Feng |
| collection | DOAJ |
| description | Abstract Pseudorabies virus (PRV) causes viral encephalitis, a devastating disease with high mortality worldwide. Curcumin (CUR) can reduce inflammatory damage by altering the phenotype of microglia; however, whether and how these changes mediate resistance to PRV-induced encephalitis is still unclear. In this study, BV2 cells were infected with/without PRV for 24 h and further treated with/without CUR for 24 h. The results indicated that CUR promoted the polarization of PRV-infected BV2 cells from the M1 phenotype to the M2 phenotype and reversed PRV-induced mitochondrial dysfunction. Furthermore, M1 BV2 cell secretions induced signalling pathways leading to apoptosis in PC-12 neuronal cells, and this effect was abrogated by the secretions of M2 BV2 cells. RNA sequencing and bioinformatics analysis predicted that this phenotypic shift may be due to changes in energy metabolism. Furthermore, Western blot analysis showed that CUR inhibited the increase in AMP-activated protein kinase (AMPK) phosphorylation, glycolysis, and triacylglycerol synthesis and the reduction in oxidative phosphorylation induced by PRV infection. Moreover, the ATP levels in M2 BV2 cells were higher than those in M1 cells. Furthermore, CUR prevented the increase in mortality, elevated body temperature, slowed growth, nervous system excitation, brain tissue congestion, vascular cuffing, and other symptoms of PRV-induced encephalitis in vivo. Thus, this study demonstrated that CUR protected against PRV-induced viral encephalitis by switching the phenotype of BV2 cells, thereby protecting neurons from inflammatory injury, and this effect was mediated by improving mitochondrial function and the AMPK/NF-κB p65-energy metabolism-related pathway. |
| first_indexed | 2024-04-09T22:42:56Z |
| format | Article |
| id | doaj.art-b787b4e52bd24cc49a40187d3d7622c8 |
| institution | Directory Open Access Journal |
| issn | 1297-9716 |
| language | English |
| last_indexed | 2024-04-09T22:42:56Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Veterinary Research |
| spelling | doaj.art-b787b4e52bd24cc49a40187d3d7622c82023-03-22T12:04:10ZengBMCVeterinary Research1297-97162023-03-0154112010.1186/s13567-023-01149-xCurcumin-dependent phenotypic transformation of microglia mediates resistance to pseudorabies-induced encephalitisLuqiu Feng0Guodong Luo1Yuhang Li2Chen Zhang3Yuxuan Liu4Yanqing Liu5Hongyue Chen6Daoling He7Yan Zhu8Ling Gan9College of Veterinary Medicine, Southwest UniversityCollege of Veterinary Medicine, Southwest UniversityCollege of Veterinary Medicine, Southwest UniversityCollege of Veterinary Medicine, Southwest UniversityCollege of Veterinary Medicine, Southwest UniversityCollege of Veterinary Medicine, Southwest UniversityChongqing General Station of Animal Husbandry Technology PromotionChongqing General Station of Animal Husbandry Technology PromotionChongqing General Station of Animal Husbandry Technology PromotionCollege of Veterinary Medicine, Southwest UniversityAbstract Pseudorabies virus (PRV) causes viral encephalitis, a devastating disease with high mortality worldwide. Curcumin (CUR) can reduce inflammatory damage by altering the phenotype of microglia; however, whether and how these changes mediate resistance to PRV-induced encephalitis is still unclear. In this study, BV2 cells were infected with/without PRV for 24 h and further treated with/without CUR for 24 h. The results indicated that CUR promoted the polarization of PRV-infected BV2 cells from the M1 phenotype to the M2 phenotype and reversed PRV-induced mitochondrial dysfunction. Furthermore, M1 BV2 cell secretions induced signalling pathways leading to apoptosis in PC-12 neuronal cells, and this effect was abrogated by the secretions of M2 BV2 cells. RNA sequencing and bioinformatics analysis predicted that this phenotypic shift may be due to changes in energy metabolism. Furthermore, Western blot analysis showed that CUR inhibited the increase in AMP-activated protein kinase (AMPK) phosphorylation, glycolysis, and triacylglycerol synthesis and the reduction in oxidative phosphorylation induced by PRV infection. Moreover, the ATP levels in M2 BV2 cells were higher than those in M1 cells. Furthermore, CUR prevented the increase in mortality, elevated body temperature, slowed growth, nervous system excitation, brain tissue congestion, vascular cuffing, and other symptoms of PRV-induced encephalitis in vivo. Thus, this study demonstrated that CUR protected against PRV-induced viral encephalitis by switching the phenotype of BV2 cells, thereby protecting neurons from inflammatory injury, and this effect was mediated by improving mitochondrial function and the AMPK/NF-κB p65-energy metabolism-related pathway.https://doi.org/10.1186/s13567-023-01149-xBV2CurcuminPRVphenotypeAMPKmitochondria |
| spellingShingle | Luqiu Feng Guodong Luo Yuhang Li Chen Zhang Yuxuan Liu Yanqing Liu Hongyue Chen Daoling He Yan Zhu Ling Gan Curcumin-dependent phenotypic transformation of microglia mediates resistance to pseudorabies-induced encephalitis Veterinary Research BV2 Curcumin PRV phenotype AMPK mitochondria |
| title | Curcumin-dependent phenotypic transformation of microglia mediates resistance to pseudorabies-induced encephalitis |
| title_full | Curcumin-dependent phenotypic transformation of microglia mediates resistance to pseudorabies-induced encephalitis |
| title_fullStr | Curcumin-dependent phenotypic transformation of microglia mediates resistance to pseudorabies-induced encephalitis |
| title_full_unstemmed | Curcumin-dependent phenotypic transformation of microglia mediates resistance to pseudorabies-induced encephalitis |
| title_short | Curcumin-dependent phenotypic transformation of microglia mediates resistance to pseudorabies-induced encephalitis |
| title_sort | curcumin dependent phenotypic transformation of microglia mediates resistance to pseudorabies induced encephalitis |
| topic | BV2 Curcumin PRV phenotype AMPK mitochondria |
| url | https://doi.org/10.1186/s13567-023-01149-x |
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