Neuroendocrinology
Original Paper
Beta-Endorphin Ameliorates Synovial Cell Hyperfunction in the Collagen-Induced Arthritis Rat Model by Specific Downregulation of NF-kappa B ActivityYin H.a, · Zhang F.a, · Yu M.a · Cheng H.b · Lin J.d · Gao Y.d · Han B.c · Zhu L.dDepartments of aRheumatology and Clinical Immunology, and cHaematology, Peking Union Medical College Hospital, Beijing, bDepartment of Biochemistry, Medical College of Yangzhou University, Yangzhou Jiangsu, and dDepartment of Immunology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China
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Article / Publication Details
Received: October 22, 2004
Accepted: December 23, 2004
Published online: May 26, 2005
Issue release date: May 2005
Number of Print Pages: 9
Number of Figures: 8
Number of Tables: 4
ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)
For additional information: https://www.karger.com/NEN
Abstract
Objectives: To observe the multiple immunoregulating effects of β-endorphin (β-END) on synovium cells of collagen-induced arthritis (CIA) in rats and to determine whether the regulation involves the transcriptional factor-ĸB (NF-ĸB) signal pathway. Methods: CIA was induced in female Wistar rats by immunization with native bovine type-II collagen emulsified with complete Freund’s adjuvant. Synovial cells in the knees of the CIA rats were cultivated, and the effects of β-END, β-END receptor inhibitor (naloxone, Nal) in proliferation and apoptosis of the synovial cells were assayed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, flow cytometry, and DNA integrity, respectively. The effects of β-END and Nal on mRNA expression of several cytokines in the synovial cells, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, regulated upon activation normal T-cell expressed and secreted (RANTES), inducible nitric oxide synthase (iNOS), matrix metalloproteinase-2 (MMP-2) and MMP-9 were estimated by quantitative reverse transcription-polymerase chain reaction. Effects of β-END and Nal on NF-ĸB activity were analyzed using luciferase gene reporter assays. The effects of β-END and Nal on p65NF-ĸB expression of the synovial cells were examined using Western blot. Results: 75% of the rats were demonstrated to have established the CIA model successfully. β-END was shown to exert multiple effects on synovial cells of CIA rats including decreased proliferation, induced apoptosis, and downregulation of TNF-α, IL-1β, IL-6, RANTES, iNOS, MMP-2 and MMP-9 mRNA expression. β-END seemed to play an immunoregulating role by downregulating the activity and expression of NF-ĸB. It was found that the β-END receptor blockage could counteract all the effects. Conclusions: β-END ameliorates synovial cell functions of CIA rats through binding with receptors and downregulating the NF-ĸB signal pathway. This suggests that β-END, by blocking the activity and expression of NF-ĸB, is a potential anti-inflammatory and anti-rheumatic agent against CIA.
© 2005 S. Karger AG, Basel
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Article / Publication Details
Received: October 22, 2004
Accepted: December 23, 2004
Published online: May 26, 2005
Issue release date: May 2005
Number of Print Pages: 9
Number of Figures: 8
Number of Tables: 4
ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)
For additional information: https://www.karger.com/NEN
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