title: Quercetin inhibits IL-1β-induced proliferation and production of MMPs, COX-2, and PGE2 by rheumatoid synovial fibroblast.
abstract: This study was aimed to determine the effects of quercetin on the interleukin-1β (IL-1β)-induced proliferation of rheumatoid synovial fibroblasts (RASFs) and production of matrix metalloproteinases (MMPs), cyclooxygenase (COX), and prostaglandin E2 (PGE2) by RASFs. The proliferation and apoptosis of RASFs was evaluated with CCK-8 reagent and flow cytometry in the presence of IL-1with CCK-8 reagquercetin. The expression of MMPs, IL-1β enhanced the expression of MMP-1, MMP-3, tissue inhibitor of metalloproteinase (TIMP)-1, COXs, PGE2, and intracellular mitogen-activated protein kinase (MAPK) signalings including phosphorylated extracellular signal-regulated kinase (p-ERK), p-p38, phosphorylated c-Jun N-terminal kinase (p-JNK), and nuclear factor kB (NF-kB) were examined by immunoblotting or semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) in conditions as described above. Quercetin inhibits unstimulated and IL-1β-induced proliferation of RASFs and MMP-1, 3, COX-2 messenger ribonucleic acid and protein expression, PGE2 production induced with IL-1β. Quercetin also inhibits the phosphorylation of ERK-1/2, p38, JNK and activation of NF-kB by IL-1ed. These results indicate that quercetin inhibits synovial fibroblasts proliferation and MMPs, COX-2, and PGE2 production, which involved joint destruction in rheumatoid arthritis (RA), and suggest that it might be a new therapeutic agent for management of RA.
authors.affiliation: Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk, 561-712, South Korea.
authors.forename: Myung-Soon
authors.initials: MS
authors.lastname: Sung
authors.forename: Eun-Gyeong
authors.initials: EG
authors.lastname: Lee
authors.forename: Hyun-Soon
authors.initials: HS
authors.lastname: Jeon
authors.forename: Han-Jung
authors.initials: HJ
authors.lastname: Chae
authors.forename: Seoung Ju
authors.initials: SJ
authors.lastname: Park
authors.forename: Yong Chul
authors.initials: YC
authors.lastname: Lee
authors.forename: Wan-Hee
authors.initials: WH
authors.lastname: Yoo
mesh_terms: D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D015232:Dinoprostone / Q000096:biosynthesis*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis* / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011794:Quercetin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D016328:NF-kappa B; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D011794:Quercetin; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1; D015232:Dinoprostone