Inhibitory Effects of Simvastatin on IL-33-Induced MCP-1 via the Suppression of the JNK Pathway in Human Vascular Endothelial Cells
An alarmin, interleukin (IL)-33 is a danger signal that causes inflammation, inducing chemotactic proteins such as monocyte chemoattractant protein (MCP)-1 in various cells. As statins have pleiotropic actions including anti-inflammatory properties, we investigated the effects of simvastatin on IL-3...
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/16/13015 |
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| author | Katsuyuki Umebashi Masayoshi Yamamoto Akinori Tokito Ku Sudou Yoko Takenoshita Michihisa Jougasaki |
| author_facet | Katsuyuki Umebashi Masayoshi Yamamoto Akinori Tokito Ku Sudou Yoko Takenoshita Michihisa Jougasaki |
| author_sort | Katsuyuki Umebashi |
| collection | DOAJ |
| description | An alarmin, interleukin (IL)-33 is a danger signal that causes inflammation, inducing chemotactic proteins such as monocyte chemoattractant protein (MCP)-1 in various cells. As statins have pleiotropic actions including anti-inflammatory properties, we investigated the effects of simvastatin on IL-33-induced MCP-1 expression in human umbilical vein endothelial cells (HUVECs). HUVECs were stimulated with IL-33 in the presence or absence of simvastatin. Gene expression and protein secretion of MCP-1, phosphorylation of mitogen-activated protein kinase (MAPK), nuclear translocation of phosphorylated c-Jun, and human monocyte migration were investigated. Immunocytochemical staining and Western immunoblot analysis revealed that IL-33 augmented MCP-1 protein expression in HUVECs. Real-time reverse transcription–polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) showed that IL-33 significantly increased MCP-1 mRNA and protein secretion, which were suppressed by c-jun N-terminal kinase (JNK) inhibitor SP600125 and p38 MAPK inhibitor SB203580. Simvastatin inhibited IL-33-induced MCP-1 mRNA, protein secretion, phosphorylation of JNK and c-Jun. Additionally, the IL-33-induced nuclear translocation of phosphorylated c-Jun and THP-1 monocyte migration were also blocked by simvastatin. This study demonstrated that IL-33 induces MCP-1 expression via the JNK and p38 MAPK pathways in HUVECs, and that simvastatin inhibits MCP-1 production by selectively suppressing JNK. Simvastatin may inhibit the progression of IL-33-induced inflammation via suppressing JNK to prevent MCP-1 production. |
| first_indexed | 2024-03-10T23:51:33Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:51:33Z |
| publishDate | 2023-08-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-88b044317b414769afcdbbf810c98a0f2023-11-19T01:34:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124161301510.3390/ijms241613015Inhibitory Effects of Simvastatin on IL-33-Induced MCP-1 via the Suppression of the JNK Pathway in Human Vascular Endothelial CellsKatsuyuki Umebashi0Masayoshi Yamamoto1Akinori Tokito2Ku Sudou3Yoko Takenoshita4Michihisa Jougasaki5Institute for Clinical Research, National Hospital Organization Kagoshima Medical Center, Kagoshima 892-0853, JapanInstitute for Clinical Research, National Hospital Organization Kagoshima Medical Center, Kagoshima 892-0853, JapanInstitute for Clinical Research, National Hospital Organization Kagoshima Medical Center, Kagoshima 892-0853, JapanInstitute for Clinical Research, National Hospital Organization Kagoshima Medical Center, Kagoshima 892-0853, JapanInstitute for Clinical Research, National Hospital Organization Kagoshima Medical Center, Kagoshima 892-0853, JapanInstitute for Clinical Research, National Hospital Organization Kagoshima Medical Center, Kagoshima 892-0853, JapanAn alarmin, interleukin (IL)-33 is a danger signal that causes inflammation, inducing chemotactic proteins such as monocyte chemoattractant protein (MCP)-1 in various cells. As statins have pleiotropic actions including anti-inflammatory properties, we investigated the effects of simvastatin on IL-33-induced MCP-1 expression in human umbilical vein endothelial cells (HUVECs). HUVECs were stimulated with IL-33 in the presence or absence of simvastatin. Gene expression and protein secretion of MCP-1, phosphorylation of mitogen-activated protein kinase (MAPK), nuclear translocation of phosphorylated c-Jun, and human monocyte migration were investigated. Immunocytochemical staining and Western immunoblot analysis revealed that IL-33 augmented MCP-1 protein expression in HUVECs. Real-time reverse transcription–polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) showed that IL-33 significantly increased MCP-1 mRNA and protein secretion, which were suppressed by c-jun N-terminal kinase (JNK) inhibitor SP600125 and p38 MAPK inhibitor SB203580. Simvastatin inhibited IL-33-induced MCP-1 mRNA, protein secretion, phosphorylation of JNK and c-Jun. Additionally, the IL-33-induced nuclear translocation of phosphorylated c-Jun and THP-1 monocyte migration were also blocked by simvastatin. This study demonstrated that IL-33 induces MCP-1 expression via the JNK and p38 MAPK pathways in HUVECs, and that simvastatin inhibits MCP-1 production by selectively suppressing JNK. Simvastatin may inhibit the progression of IL-33-induced inflammation via suppressing JNK to prevent MCP-1 production.https://www.mdpi.com/1422-0067/24/16/13015interleukin-33monocyte chemoattractant protein-1cell migrationmitogen-activated protein kinasecytokinestatins |
| spellingShingle | Katsuyuki Umebashi Masayoshi Yamamoto Akinori Tokito Ku Sudou Yoko Takenoshita Michihisa Jougasaki Inhibitory Effects of Simvastatin on IL-33-Induced MCP-1 via the Suppression of the JNK Pathway in Human Vascular Endothelial Cells International Journal of Molecular Sciences interleukin-33 monocyte chemoattractant protein-1 cell migration mitogen-activated protein kinase cytokine statins |
| title | Inhibitory Effects of Simvastatin on IL-33-Induced MCP-1 via the Suppression of the JNK Pathway in Human Vascular Endothelial Cells |
| title_full | Inhibitory Effects of Simvastatin on IL-33-Induced MCP-1 via the Suppression of the JNK Pathway in Human Vascular Endothelial Cells |
| title_fullStr | Inhibitory Effects of Simvastatin on IL-33-Induced MCP-1 via the Suppression of the JNK Pathway in Human Vascular Endothelial Cells |
| title_full_unstemmed | Inhibitory Effects of Simvastatin on IL-33-Induced MCP-1 via the Suppression of the JNK Pathway in Human Vascular Endothelial Cells |
| title_short | Inhibitory Effects of Simvastatin on IL-33-Induced MCP-1 via the Suppression of the JNK Pathway in Human Vascular Endothelial Cells |
| title_sort | inhibitory effects of simvastatin on il 33 induced mcp 1 via the suppression of the jnk pathway in human vascular endothelial cells |
| topic | interleukin-33 monocyte chemoattractant protein-1 cell migration mitogen-activated protein kinase cytokine statins |
| url | https://www.mdpi.com/1422-0067/24/16/13015 |
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