The Histone Deacetylase Inhibitors MS-275 and SAHA Suppress the p38 Mitogen-Activated Protein Kinase Signaling Pathway and Chemotaxis in Rheumatoid Arthritic Synovial Fibroblastic E11 Cells
MS-275 (entinostat) and SAHA (vorinostat), two histone deacetylase (HDAC) inhibitors currently in oncological trials, have displayed potent anti-rheumatic activities in rodent models of rheumatoid arthritis (RA). To further elucidate their anti-inflammatory mechanisms, the impact of MS-275 and SAHA...
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MDPI AG
2013-11-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/18/11/14085 |
| _version_ | 1819114241097990144 |
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| author | Hai-Shu Lin Yoshiya Tanaka Paul C Ho Qiu-Yi Choo |
| author_facet | Hai-Shu Lin Yoshiya Tanaka Paul C Ho Qiu-Yi Choo |
| author_sort | Hai-Shu Lin |
| collection | DOAJ |
| description | MS-275 (entinostat) and SAHA (vorinostat), two histone deacetylase (HDAC) inhibitors currently in oncological trials, have displayed potent anti-rheumatic activities in rodent models of rheumatoid arthritis (RA). To further elucidate their anti-inflammatory mechanisms, the impact of MS-275 and SAHA on the p38 mitogen-activated protein kinase (MAPK) signaling pathway and chemotaxis was assessed in human rheumatoid arthritic synovial fibroblastic E11 cells. MS-275 and SAHA significantly suppressed the expression of p38α MAPK, but induced the expression of MAPK phosphatase-1 (MKP-1), an endogenous suppressor of p38α in E11 cells. At the same time, the association between p38α and MKP-1 was up-regulated and consequently, the activation (phosphorylation) of p38α was inhibited. Moreover, MS-275 and SAHA suppressed granulocyte chemotactic protein-2 (GCP-2), monocyte chemotactic protein-2 (MCP-2) and macrophage migration inhibitory factor (MIF) in E11 cells in a concentration-dependent manner. Subsequently, E11-driven migration of THP-1 and U937 monocytes was inhibited. In summary, suppression of the p38 MAPK signaling pathway and chemotaxis appear to be important anti-rheumatic mechanisms of action of these HDAC inhibitors. |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-22T04:42:10Z |
| publishDate | 2013-11-01 |
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| spelling | doaj.art-3105e318911f47efa03509fdbbda1c882022-12-21T18:38:42ZengMDPI AGMolecules1420-30492013-11-011811140851409510.3390/molecules181114085The Histone Deacetylase Inhibitors MS-275 and SAHA Suppress the p38 Mitogen-Activated Protein Kinase Signaling Pathway and Chemotaxis in Rheumatoid Arthritic Synovial Fibroblastic E11 CellsHai-Shu LinYoshiya TanakaPaul C HoQiu-Yi ChooMS-275 (entinostat) and SAHA (vorinostat), two histone deacetylase (HDAC) inhibitors currently in oncological trials, have displayed potent anti-rheumatic activities in rodent models of rheumatoid arthritis (RA). To further elucidate their anti-inflammatory mechanisms, the impact of MS-275 and SAHA on the p38 mitogen-activated protein kinase (MAPK) signaling pathway and chemotaxis was assessed in human rheumatoid arthritic synovial fibroblastic E11 cells. MS-275 and SAHA significantly suppressed the expression of p38α MAPK, but induced the expression of MAPK phosphatase-1 (MKP-1), an endogenous suppressor of p38α in E11 cells. At the same time, the association between p38α and MKP-1 was up-regulated and consequently, the activation (phosphorylation) of p38α was inhibited. Moreover, MS-275 and SAHA suppressed granulocyte chemotactic protein-2 (GCP-2), monocyte chemotactic protein-2 (MCP-2) and macrophage migration inhibitory factor (MIF) in E11 cells in a concentration-dependent manner. Subsequently, E11-driven migration of THP-1 and U937 monocytes was inhibited. In summary, suppression of the p38 MAPK signaling pathway and chemotaxis appear to be important anti-rheumatic mechanisms of action of these HDAC inhibitors.http://www.mdpi.com/1420-3049/18/11/14085histone deacetylase inhibitorrheumatoid arthritisMS-275SAHAp38 MAPKMKP-1chemotaxis |
| spellingShingle | Hai-Shu Lin Yoshiya Tanaka Paul C Ho Qiu-Yi Choo The Histone Deacetylase Inhibitors MS-275 and SAHA Suppress the p38 Mitogen-Activated Protein Kinase Signaling Pathway and Chemotaxis in Rheumatoid Arthritic Synovial Fibroblastic E11 Cells Molecules histone deacetylase inhibitor rheumatoid arthritis MS-275 SAHA p38 MAPK MKP-1 chemotaxis |
| title | The Histone Deacetylase Inhibitors MS-275 and SAHA Suppress the p38 Mitogen-Activated Protein Kinase Signaling Pathway and Chemotaxis in Rheumatoid Arthritic Synovial Fibroblastic E11 Cells |
| title_full | The Histone Deacetylase Inhibitors MS-275 and SAHA Suppress the p38 Mitogen-Activated Protein Kinase Signaling Pathway and Chemotaxis in Rheumatoid Arthritic Synovial Fibroblastic E11 Cells |
| title_fullStr | The Histone Deacetylase Inhibitors MS-275 and SAHA Suppress the p38 Mitogen-Activated Protein Kinase Signaling Pathway and Chemotaxis in Rheumatoid Arthritic Synovial Fibroblastic E11 Cells |
| title_full_unstemmed | The Histone Deacetylase Inhibitors MS-275 and SAHA Suppress the p38 Mitogen-Activated Protein Kinase Signaling Pathway and Chemotaxis in Rheumatoid Arthritic Synovial Fibroblastic E11 Cells |
| title_short | The Histone Deacetylase Inhibitors MS-275 and SAHA Suppress the p38 Mitogen-Activated Protein Kinase Signaling Pathway and Chemotaxis in Rheumatoid Arthritic Synovial Fibroblastic E11 Cells |
| title_sort | histone deacetylase inhibitors ms 275 and saha suppress the p38 mitogen activated protein kinase signaling pathway and chemotaxis in rheumatoid arthritic synovial fibroblastic e11 cells |
| topic | histone deacetylase inhibitor rheumatoid arthritis MS-275 SAHA p38 MAPK MKP-1 chemotaxis |
| url | http://www.mdpi.com/1420-3049/18/11/14085 |
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