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Sulforaphane has opposing effects on TNF-alpha stimulated and unstimulated synoviocytes.

Abstract：

INTRODUCTION:Rheumatoid arthritis (RA) is characterized by progressive inflammation associated with rampantly proliferating synoviocytes and joint destruction due to oxidative stress. Recently, we described nuclear factor erythroid 2-related factor 2 (Nrf2) as a major requirement for limiting cartilage destruction. NF-κB and AP-1 are the main transcription factors triggering the inflammatory progression in RA. We used sulforaphane, an isothiocyanate, which is both an Nrf2 inducer and a NF-κB and AP-1 inhibitor. METHODS:Cultured synoviocytes were stimulated with sulforaphane (SFN) with or without TNF-α pre-treatment. NF-κB, AP-1, and Nrf2 activation was investigated via dual luciferase reporter gene assays. Matrix metalloproteinases (MMPs) were measured via zymography and luminex technique. Cytokine levels were detected using ELISA. Cell viability, apoptosis and caspase activity were studied. Cell proliferation was analysed by real-time cell analysis. RESULTS:SFN treatment decreased inflammation and proliferation dose-dependently in TNF-α-stimulated synoviocytes. SFN did not reduce MMP-3 and MMP-9 activity or expression significantly. Interestingly, we demonstrated that SFN has opposing effects on naïve and TNF-α-stimulated synoviocytes. In naïve cells, SFN activated the cytoprotective transcription factor Nrf2. In marked contrast to this, SFN induced apoptosis in TNF-α-pre-stimulated synoviocytes. CONCLUSIONS:We were able to show that SFN treatment acts contrary on naïve and inflammatory synoviocytes. SFN induces the cytoprotective transcription factor Nrf2 in naïve synoviocytes, whereas it induces apoptosis in inflamed synoviocytes. These findings indicate that the use of sulforaphane might be considered as an adjunctive therapeutic strategy to combat inflammation, pannus formation, and cartilage destruction in RA.

journal_name

Arthritis Res Ther

journal_title

Arthritis research & therapy

authors

Fragoulis A,Laufs J,Müller S,Soppa U,Siegl S,Reiss LK,Tohidnezhad M,Rosen C,Tenbrock K,Varoga D,Lippross S,Pufe T,Wruck CJ

doi

10.1186/ar4059

subject

Has Abstract

pub_date

2012-10-27 00:00:00

pages

R220

issue

eissn

1478-6354

issn

1478-6362

pii

ar4059

journal_volume

pub_type

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Sulforaphane has opposing effects on TNF-alpha stimulated and unstimulated synoviocytes.