Caspase-1-Dependent Pyroptosis Mediates Adjuvant Activity of Platycodin D as an Adjuvant for Intramuscular Vaccines
Platycodin D (PD) is a potent adjuvant with dual Th1 and Th2 potentiating activity, but its mechanisms of action remain unclear. Here, the C2C12 myoblast cell line and mice were used as in vitro and in vivo models to identify potential signaling pathways involved in the adjuvant activity of PD. PD i...
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MDPI AG
2022-01-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/1/134 |
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| author | Liyan Zhu Ziyi Han Yanfei He Hongxiang Sun |
| author_facet | Liyan Zhu Ziyi Han Yanfei He Hongxiang Sun |
| author_sort | Liyan Zhu |
| collection | DOAJ |
| description | Platycodin D (PD) is a potent adjuvant with dual Th1 and Th2 potentiating activity, but its mechanisms of action remain unclear. Here, the C2C12 myoblast cell line and mice were used as in vitro and in vivo models to identify potential signaling pathways involved in the adjuvant activity of PD. PD induced a transient cytotoxicity and inflammatory response in the C2C12 cells and in mouse quadricep muscles. A comparative analysis of microarray data revealed that PD induced similar gene expression profiles in the C2C12 cells and in the quadricep muscles, and triggered rapid regulation of death, immune, and inflammation-related genes, both in vivo and in vitro. It was further demonstrated that caspase-1-dependent pyroptosis was involved in the PD-induced cytotoxicity and inflammatory response in the C2C12 cells via the Ca<sup>2+</sup>–c-jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK)–NLR family pyrin domain containing 3 (NLRP3) inflammasome signaling pathway. Consistently, the in vivo analysis revealed that a local blockage of NLRP3 and caspase-1 inhibited PD-induced cytokine production and immune cell recruitment at the injection site, and impaired the adjuvant activity of PD on antigen-specific immune responses to model antigen ovalbumin (OVA) in mice. These findings identified the caspase-1-dependent adjuvanticity of PD and expanded the current knowledge on the mechanisms of action of saponin-based adjuvants. |
| first_indexed | 2024-03-10T03:45:41Z |
| format | Article |
| id | doaj.art-ba3e031c1de74c839bdb35f3ee93b40b |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T03:45:41Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
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| spelling | doaj.art-ba3e031c1de74c839bdb35f3ee93b40b2023-11-23T11:20:42ZengMDPI AGCells2073-44092022-01-0111113410.3390/cells11010134Caspase-1-Dependent Pyroptosis Mediates Adjuvant Activity of Platycodin D as an Adjuvant for Intramuscular VaccinesLiyan Zhu0Ziyi Han1Yanfei He2Hongxiang Sun3Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, ChinaDepartment of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, ChinaDepartment of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, ChinaDepartment of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, ChinaPlatycodin D (PD) is a potent adjuvant with dual Th1 and Th2 potentiating activity, but its mechanisms of action remain unclear. Here, the C2C12 myoblast cell line and mice were used as in vitro and in vivo models to identify potential signaling pathways involved in the adjuvant activity of PD. PD induced a transient cytotoxicity and inflammatory response in the C2C12 cells and in mouse quadricep muscles. A comparative analysis of microarray data revealed that PD induced similar gene expression profiles in the C2C12 cells and in the quadricep muscles, and triggered rapid regulation of death, immune, and inflammation-related genes, both in vivo and in vitro. It was further demonstrated that caspase-1-dependent pyroptosis was involved in the PD-induced cytotoxicity and inflammatory response in the C2C12 cells via the Ca<sup>2+</sup>–c-jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK)–NLR family pyrin domain containing 3 (NLRP3) inflammasome signaling pathway. Consistently, the in vivo analysis revealed that a local blockage of NLRP3 and caspase-1 inhibited PD-induced cytokine production and immune cell recruitment at the injection site, and impaired the adjuvant activity of PD on antigen-specific immune responses to model antigen ovalbumin (OVA) in mice. These findings identified the caspase-1-dependent adjuvanticity of PD and expanded the current knowledge on the mechanisms of action of saponin-based adjuvants.https://www.mdpi.com/2073-4409/11/1/134platycodin Dadjuvantpyroptosiscaspase-1JNK and p38 MAPK signalinginflammatory response |
| spellingShingle | Liyan Zhu Ziyi Han Yanfei He Hongxiang Sun Caspase-1-Dependent Pyroptosis Mediates Adjuvant Activity of Platycodin D as an Adjuvant for Intramuscular Vaccines Cells platycodin D adjuvant pyroptosis caspase-1 JNK and p38 MAPK signaling inflammatory response |
| title | Caspase-1-Dependent Pyroptosis Mediates Adjuvant Activity of Platycodin D as an Adjuvant for Intramuscular Vaccines |
| title_full | Caspase-1-Dependent Pyroptosis Mediates Adjuvant Activity of Platycodin D as an Adjuvant for Intramuscular Vaccines |
| title_fullStr | Caspase-1-Dependent Pyroptosis Mediates Adjuvant Activity of Platycodin D as an Adjuvant for Intramuscular Vaccines |
| title_full_unstemmed | Caspase-1-Dependent Pyroptosis Mediates Adjuvant Activity of Platycodin D as an Adjuvant for Intramuscular Vaccines |
| title_short | Caspase-1-Dependent Pyroptosis Mediates Adjuvant Activity of Platycodin D as an Adjuvant for Intramuscular Vaccines |
| title_sort | caspase 1 dependent pyroptosis mediates adjuvant activity of platycodin d as an adjuvant for intramuscular vaccines |
| topic | platycodin D adjuvant pyroptosis caspase-1 JNK and p38 MAPK signaling inflammatory response |
| url | https://www.mdpi.com/2073-4409/11/1/134 |
| work_keys_str_mv | AT liyanzhu caspase1dependentpyroptosismediatesadjuvantactivityofplatycodindasanadjuvantforintramuscularvaccines AT ziyihan caspase1dependentpyroptosismediatesadjuvantactivityofplatycodindasanadjuvantforintramuscularvaccines AT yanfeihe caspase1dependentpyroptosismediatesadjuvantactivityofplatycodindasanadjuvantforintramuscularvaccines AT hongxiangsun caspase1dependentpyroptosismediatesadjuvantactivityofplatycodindasanadjuvantforintramuscularvaccines |