Beta-Endorphin Ameliorates Synovial Cell Hyperfunction in the Collagen-Induced Arthritis Rat Model by Specific Downregulation of NF-kappa B Activity.

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-κB (NF-κB) 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-κB activity were analyzed using luciferase gene reporter assays. The effects of β-END and Nal on p65NF-κB 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-κB. 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-κB signal pathway. This suggests that β-END, by blocking the activity and expression of NF-κB, is a potential anti-inflammatory and anti-rheumatic agent against CIA. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]