title: 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: Graduate School of East-West Medical Science, Kyung Hee University, Korea.
authors: Mi-Kyoung
authors: MK
authors: Ha
authors: Young Hoon
authors: YH
authors: Song
authors: Soo-Jin
authors: SJ
authors: Jeong
authors: Hyo-Jung
authors: HJ
authors: Lee
authors: Ji Hoon
authors: JH
authors: Jung
authors: Bonglee
authors: B
authors: Kim
authors: Hyo Sook
authors: HS
authors: Song
authors: Jeong-Eun
authors: JE
authors: Huh
authors: Sung-Hoon
authors: SH
authors: Kim
mesh_terms: D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000473:pathology; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors; D024202:Electrophoretic Mobility Shift Assay; D004642:Emodin / Q000494:pharmacology*; D004789:Enzyme Activation; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors*; D053583:Interleukin-1beta / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D056284:Histone Deacetylase 1; D004642:Emodin