Sulforaphane inhibits inflammatory responses of primary human T-cells by increasing ROS and depleting glutathione

• Verfasst von: Liang, Jie [VerfasserIn]
• Verfasst von: Jahraus, Beate [VerfasserIn]
• Verfasst von: Balta, Emre [VerfasserIn]
• Verfasst von: Ziegler, Jacqueline D. [VerfasserIn]
• Verfasst von: Hübner, Katrin [VerfasserIn]
• Verfasst von: Blank, Norbert [VerfasserIn]
• Verfasst von: Niesler, Beate [VerfasserIn]
• Verfasst von: Wabnitz, Guido H. [VerfasserIn]
• Verfasst von: Samstag, Yvonne [VerfasserIn]
• Titel: Sulforaphane inhibits inflammatory responses of primary human T-cells by increasing ROS and depleting glutathione
• Verf.angabe: Jie Liang, Beate Jahraus, Emre Balta, Jacqueline D. Ziegler, Katrin Hübner, Norbert Blank, Beate Niesler, Guido H. Wabnitz and Yvonne Samstag
• E-Jahr: 2018
• Jahr: 14 November 2018
• Umfang: 17 S.
• Fussnoten: Gesehen am 06.12.2018
• Titel Quelle: Enthalten in: Frontiers in immunology
• Ort Quelle: Lausanne : Frontiers Media, 2010
• Jahr Quelle: 2018
• Band/Heft Quelle: 9(2018), Artikel-ID 2584
• ISSN Quelle: 1664-3224
• DOI: doi:10.3389/fimmu.2018.02584
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Glutathione
• Sach-SW: Primary human T-cells
• Sach-SW: Reactive Oxygen Species
• Sach-SW: Rheumatoid arthritis
• Sach-SW: Sulforaphane
• Sach-SW: Th17
• K10plus-PPN: 1584917741
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

Abstract

The activity and function of T-cells are influenced by the intra- and extracellular redox milieu. Oxidative stress induces hypo-responsiveness of untransformed T-cells. Vice versa increased glutathione (GSH) levels or decreased levels of reactive oxygen species (ROS) prime T-cell metabolism for inflammation, e.g. in rheumatoid arthritis (RA). Therefore, balancing the T-cell redox milieu may represent a promising new option for therapeutic immune modulation. Here we show that sulforaphane (SFN), a compound derived from plants of the Brassicaceae family, e.g. broccoli, induces a pro-oxidative state in untransformed human T-cells of healthy donors or RA patients. This manifested as an increase of intracellular ROS and a marked decrease of GSH. Consistently, increased global cysteine sulfenylation was detected. Importantly, a major target for SFN-mediated protein oxidation was STAT3, a transcription factor involved in the regulation of TH17-related genes. Accordingly, SFN significantly inhibited the activation of untransformed human T-cells derived from healthy donors or RA patients, and specifically downregulated the the transcription factor RORt expression of the TH17-related cytokines IL-17A, IL-17F, and IL-22, which play a major role within the pathophysiology of many chronic inflammatory/autoimmune diseases. The inhibitory effects of SFN could be abolished by exogenous supplied GSH and the GSH replenishing antioxidant N-acetyl-cysteine (NAC). Together, our study provides mechanistic insights into the mode of action of the natural substance sulforaphane. It specifically exerts TH17 prone immunosuppressive effects on untransformed human T-cells by decreasing GSH and accumulation of ROS. Thus, SFN may offer novel clinical options for the treatment of TH17 related chronic inflammatory/autoimmune diseases such as rheumatoid arthritis.