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Quercetin Inhibits IL-1β-Induced Proliferation and Production of MMPs, COX-2, and PGE2 by Rheumatoid Synovial Fibroblast

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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.

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ACKNOWLEDGMENTS

This study was supported by a grant of the Korea Healthcare Technology R&D Project, the Ministry for Health, Welfare, and Family Affairs, Republic of Korea (A084144).

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Authors and Affiliations

  1. Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk, 561-712, South Korea

    Myung-Soon Sung, Eun-Gyeong Lee, Hyun-Soon Jeon, Seoung Ju Park, Yong Chul Lee & Wan-Hee Yoo

  2. Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Jeonju, Jeonbuk, 561-712, South Korea

    Myung-Soon Sung, Eun-Gyeong Lee, Hyun-Soon Jeon, Seoung Ju Park, Yong Chul Lee & Wan-Hee Yoo

  3. Department of Pharmacology, Chonbuk National University Medical School, Jeonju, Jeonbuk, 561-712, South Korea

    Han-Jung Chae

  4. Division of Rheumatology, Department of Internal Medicine, Chonbuk National University Medical School and Research Institute of Clinical Medicine, San 2-20 Geumam-dong, Deokjin-gu, Jeonju, Jeonbuk, 561-180, South Korea

    Wan-Hee Yoo

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  1. Myung-Soon Sung
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Correspondence to Wan-Hee Yoo.

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Myung-Soon Sung and Eun-Gyeong Lee contributed equally to this work.

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Sung, MS., Lee, EG., Jeon, HS. et al. Quercetin Inhibits IL-1β-Induced Proliferation and Production of MMPs, COX-2, and PGE2 by Rheumatoid Synovial Fibroblast. Inflammation 35, 1585–1594 (2012). https://doi.org/10.1007/s10753-012-9473-2

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