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Translocator protein (18 kDa) (TSPO) ligands activate Nrf2 signaling and attenuate inflammatory responses and oxidative stress in human retinal pigment epithelial cells.
Rashid, Khalid; Verhoyen, Mathilde; Taiwo, Moyinoluwa; Langmann, Thomas.
Afiliación
  • Rashid K; Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931, Cologne, Germany. Electronic address: krashid@mednet.ucla.edu.
  • Verhoyen M; Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931, Cologne, Germany; University of Namur, Faculty of Medicine, Biomedical Sciences Department, 61 -5000, Namur, Belgium. Electronic address:
  • Taiwo M; Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931, Cologne, Germany. Electronic address: moyinoluwa.taiwo@uk-koeln.de.
  • Langmann T; Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), 50931, Cologne, Germany. Electronic address: thomas.langmann@uk-koeln.de.
Biochem Biophys Res Commun ; 528(2): 261-268, 2020 07 23.
Article en En | MEDLINE | ID: mdl-32482385
Degeneration of the retinal pigment epithelium (RPE) is a hallmark of atrophic age-related macular degeneration (AMD). Microglia mediated inflammatory responses and oxidative stress are critical pathophysiological processes in the onset and progression of RPE degeneration. Given the central role of the RPE, strategies to protect these cells from damage caused by oxidative stress and inflammation present a promising therapeutic approach to mitigate AMD. Ligands for the translocator protein (18 kDa) (TSPO) have been shown to confer protection against retinal inflammatory responses and neurodegeneration by acting primarily through retinal glia. However, despite RPE cells demonstrating strong TSPO expression, it remains unclear whether TSPO ligands could also inhibit inflammatory responses of RPE cells. Here, we investigated the influence of three different TSPO ligands XBD173, PK11195 and Ro5-4864 on inflammatory responses in human ARPE-19 cells triggered by supernatants from reactive human microglial cells and the lysosomal destabilizer, LLOMe. Our findings revealed that TSPO ligands significantly inhibited proinflammatory gene expression, inflammasome-mediated caspase-1 activation, lipid accumulation and intracellular ROS levels in stressed ARPE-19 cells. Notably, TSPO ligands induced activation of Nrf2 pathway and its downstream regulated genes in ARPE-19 cells, with Hmox-1 being the most strongly upregulated gene. Collectively, our study indicates that TSPO ligands can enhance the Nrf2 antioxidant pathway in RPE cells and protect them from cellular damage resulting from inflammation and oxidative stress.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Receptores de GABA / Estrés Oxidativo / Factor 2 Relacionado con NF-E2 / Epitelio Pigmentado de la Retina / Inflamación Límite: Humans Idioma: En Revista: Biochem Biophys Res Commun Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Receptores de GABA / Estrés Oxidativo / Factor 2 Relacionado con NF-E2 / Epitelio Pigmentado de la Retina / Inflamación Límite: Humans Idioma: En Revista: Biochem Biophys Res Commun Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos