Emodin inhibits proinflammatory responses and inactivates histone deacetylase 1 in hypoxic rheumatoid synoviocytes.

Abstract

Chronic inflammation of rheumatoid arthritis (RA) is promoted by proinflammatory cytokines and closely linked to angiogenesis. In the present study, we investigated the anti-inflammatory effects of emodin (1,3,8-trihydroxy-6-methyl-anthraquinone) isolated from the root of Rheum palmatum L. in interleukin 1 beta (IL-1β) and lipopolysaccharide (LPS)-stimulated RA synoviocytes under hypoxia. Emodin significantly inhibited IL-1β and LPS-stimulated proliferation of RA synoviocytes in a dose-dependent manner under hypoxic condition. Also, enzyme linked immunosorbent assay (ELISA) revealed that emodin significantly reduced the production of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α), IL-6 and IL-8], mediators [prostagladin E(2) (PGE(2)), matrix metalloproteinase (MMP)-1 and MMP-13] and vascular endothelial growth factor (VEGF) as an angiogenesis biomarker in IL-1β and LPS-treated synoviocytes under hypoxia. Consistently, emodin attenuated the expression of cyclooxygenase 2 (COX-2), VEGF, hypoxia inducible factor 1 alpha (HIF-1α), MMP-1 and MMP-13 at mRNA level in IL-1β and LPS-treated synoviocytes under hypoxia. Furthermore, emodin reduced histone deacetylase (HDAC) activity as well as suppressed the expression of HDAC1, but not HDAC2 in IL-1β and LPS-treated synoviocytes under hypoxia. Overall, these findings suggest that emodin inhibits proinflammatory cytokines and VEGF productions, and HDAC1 activity in hypoxic RA synoviocytes.

• Authors: Mi-Kyoung Ha, Young Hoon Song, Soo-Jin Jeong, Hyo-Jung Lee, Ji Hoon Jung, Bonglee Kim, Hyo Sook Song, Jeong-Eun Huh, Sung-Hoon Kim
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 34 Issue 9 Pg. 1432-7 ( 2011) ISSN: 1347-5215 [Electronic] Japan
• PMID: 21881229 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Inflammation Mediators
• Interleukin-1beta
• Histone Deacetylase 1
• Emodin

Topics

• Arthritis, Rheumatoid (enzymology, pathology)
• Blotting, Western
• Cell Proliferation (drug effects)
• Cells, Cultured
• Cytokines (antagonists & inhibitors)
• Electrophoretic Mobility Shift Assay
• Emodin (pharmacology)
• Enzyme Activation
• Histone Deacetylase 1 (metabolism)
• Humans
• Inflammation (prevention & control)
• Inflammation Mediators (antagonists & inhibitors)
• Interleukin-1beta (pharmacology)
• Reverse Transcriptase Polymerase Chain Reaction
• Synovial Membrane (drug effects, enzymology, pathology)