IntroductionRheumatoid 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.MethodsCultured 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.ResultsSFN 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.ConclusionsWe 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.
Zusammenfassung Anamnese und klinischer Befund Bis zum 24.02.2020 vereinzelt auftretende, nicht schwerverlaufende SARS-CoV-2-Infektionen in Deutschland. Notfallmäßige Vorstellung eines Ehepaars in der zentralen Notaufnahme. Der Mann gibt an, seit 7 Tagen an hochfieberhaften Temperaturen, trockenem Reizhusten und körperlicher Schwäche zu leiden, während die Ehefrau ähnliche Symptome in milderer Ausprägung bietet. In der klinischen Untersuchung fallen feinblasige Rasselgeräusche über beiden Lungen beider Patienten und eine respiratorische Insuffizienz des Ehemanns auf. Untersuchungen und Diagnose Laborserologisch Erhöhung der Inflammationsparameter sowie der Transaminasen und der Laktatdehydrogenase. Röntgenologisch pulmonale Infiltrate unterschiedlicher Ausprägung bei beiden Patienten. Im weiteren Verlauf Nachweis einer SARS-CoV-2-Infektion der Ehepartner mit schwerem Verlauf beim männlichen Patienten. Therapie und Verlauf Intubation und Beatmung des männlichen Patienten bei mittelschwerem ARDS mit langer intensivmedizinischer Behandlung. Genesung der weiblichen Patientin unter Sauerstofftherapie. Diskussion Diese beiden Fälle zeigen den Ausgangspunkt einer endemischen Verbreitung von SARS-CoV-2 im Landkreis Heinsberg (NRW) und bis zu diesem Zeitpunkt den ersten Fall eines lebensbedrohlichen Verlaufs in Deutschland.
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