Next Article in Journal
Bioactive Quinic Acid Derivatives from Ageratina adenophora
Previous Article in Journal
Design, Synthesis and Cytotoxic Activities of Novel Aliphatic Amino-Substituted Flavonoids
Molecules 2013, 18(11), 14085-14095; doi:10.3390/molecules181114085
Article

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

1
,
1
,
2
 and
1,*
1 Department of Pharmacy, Faculty of Science, National University of Singapore, 10 Kent Ridge Crescent, 119260, Singapore 2 First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan
* Author to whom correspondence should be addressed.
Received: 29 October 2013 / Revised: 6 November 2013 / Accepted: 6 November 2013 / Published: 14 November 2013
View Full-Text   |   Download PDF [466 KB, uploaded 18 June 2014]   |  

Abstract

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.
Keywords: histone deacetylase inhibitor; rheumatoid arthritis; MS-275; SAHA; p38 MAPK; MKP-1; chemotaxis histone deacetylase inhibitor; rheumatoid arthritis; MS-275; SAHA; p38 MAPK; MKP-1; chemotaxis
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
SciFeed

Share & Cite This Article

Further Mendeley | CiteULike
Export to BibTeX |
EndNote |
RIS
MDPI and ACS Style

Choo, Q.-Y.; Ho, P.C.; Tanaka, Y.; Lin, H.-S. 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 2013, 18, 14085-14095.

View more citation formats

Related Articles

Article Metrics

For more information on the journal, click here

Comments

[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert