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The AhR ligand 2, 2'-aminophenyl indole (2AI) regulates microglia homeostasis and reduces pro-inflammatory signaling.
Khan, Amir Saeed; Wolf, Anne; Langmann, Thomas.
Afiliación
  • Khan AS; Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, University of Cologne, Faculty of Medicine and University Hospital Cologne, 50931, Cologne, Germany. Electronic address: amir.khan@uk-koeln.de.
  • Wolf A; Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, University of Cologne, Faculty of Medicine and University Hospital Cologne, 50931, Cologne, Germany. Electronic address: anne.wolf@uk-koeln.de.
  • Langmann T; Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, University of Cologne, Faculty of Medicine and University Hospital Cologne, 50931, Cologne, Germany; Center for Molecular Medicine, 50931, Cologne, Germany. Electronic address: thomas.langmann@uk-koeln.de.
Biochem Biophys Res Commun ; 579: 15-21, 2021 11 19.
Article en En | MEDLINE | ID: mdl-34583190
Retinal degeneration is a leading cause of visual impairment and blindness worldwide. Microglia reactivity is a hallmark of neurodegenerative diseases and a driving force for retinal cell death and disease progression. Thus, immunomodulation emerges as a potential therapeutic option. AhR deficiency is known to trigger inflammation and previous studies revealed important roles for AhR ligands in neuroprotection without focusing on microglia. Here, we investigate the anti-inflammatory and antioxidant effects of the synthetic aryl hydrocarbon receptor (AhR) ligand 2, 2'-aminophenyl indole (2AI) on microglia reactivity. We showed that 2AI potently reduced pro-inflammatory gene expression and induced antioxidant genes in activated human and murine microglia cells, in LPS-stimulated retinal explants as well as in stressed human ARPE-19 cells. 2AI also diminished LPS-induced nitric oxide (NO) release, their neurotoxic activity on photoreceptor cells, phagocytosis, and migration in murine BV-2 cells as important functional microglia parameters. siRNA-mediated knockdown of AhR partially prevented the previously observed gene regulatory effects in BV-2 cells. Our results show for the first time, that the synthetic AhR agonist 2AI regulates microglia homeostasis, highlighting AhR as a potential drug target for immunomodulatory and antioxidant therapies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Receptores de Hidrocarburo de Aril / Microglía / Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico / Indoles / Inflamación Límite: Animals / Humans Idioma: En Revista: Biochem Biophys Res Commun Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Receptores de Hidrocarburo de Aril / Microglía / Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico / Indoles / Inflamación Límite: Animals / Humans Idioma: En Revista: Biochem Biophys Res Commun Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos