Sulforaphane has opposing effects on TNF-alpha stimulated and unstimulated synoviocytes.
Sulforaphane has opposing effects on TNF-alpha stimulated and unstimulated synoviocytes.
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DOI：
10.1186/ar4059
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发表时间：
2012-10-27
影响因子：
4.9
通讯作者：
Wruck CJ
中科院分区：
文献类型：
--
作者：
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
风湿性关节炎（RA）的特征是进行性炎症与猖獗增殖的滑膜细胞和关节破坏由于氧化应激。最近，我们描述了核因子红细胞2相关因子2（Nrf 2）作为限制软骨破坏的主要要求。NF-κB和AP-1是触发RA炎症进展的主要转录因子。我们使用了萝卜硫素，一种异硫氰酸酯，它既是Nrf 2诱导剂，也是NF-κB和AP-1抑制剂。用莱菔硫烷（SFN）刺激培养的滑膜细胞，有或没有TNF-α预处理。通过双荧光素酶报告基因测定研究NF-κB、AP-1和Nrf 2活化。基质金属蛋白酶（MMPs）的测定采用酶谱法和Luminex技术。使用ELISA检测细胞因子水平。检测细胞存活率、凋亡率和caspase活性。通过实时细胞分析来分析细胞增殖。SFN处理可剂量依赖性地降低TNF-α刺激的滑膜细胞的炎症和增殖。SFN对MMP-3和MMP-9的活性和表达无明显影响。有趣的是，我们证明了SFN对幼稚和TNF-α刺激的滑膜细胞具有相反的作用。在幼稚细胞中，SFN激活了细胞保护性转录因子Nrf 2。与此形成鲜明对比的是，SFN诱导TNF-α预刺激的滑膜细胞凋亡。我们能够证明SFN治疗对幼稚和炎症性滑膜细胞起相反的作用。SFN在幼稚滑膜细胞中诱导细胞保护性转录因子Nrf 2，而在发炎滑膜细胞中诱导凋亡。这些发现表明，萝卜硫素的使用可能被认为是一种对抗RA炎症、血管翳形成和软骨破坏的连续治疗策略。
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. 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. 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. 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.
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影响因子：
6.7
作者：
Brandenburg, Lars-Ove;Kipp, Markus;Wruck, Christoph J.
通讯作者：
Wruck, Christoph J.
影响因子：
27.4
作者：
Wruck, Christoph Jan;Fragoulis, Athanassios;Pufe, Thomas
通讯作者：
Pufe, Thomas
DOI：
10.1073/pnas.172398899
发表时间：
2002-09-03
影响因子：
11.1
作者：
Dinkova-Kostova, AT;Holtzclaw, WD;Talalay, P
通讯作者：
Talalay, P
NRF2：氧化应激中的INRF2（KEAP1）信号传导。
影响因子：
7.4
作者：
Kaspar, James W.;Niture, Suryakant K.;Jaiswal, Anil K.
通讯作者：
Jaiswal, Anil K.
影响因子：
--
作者：
Kong, Jin-Sun;Yoo, Seung-Ah;Kim, Wan-Uk
通讯作者：
Kim, Wan-Uk