Universität zu Köln

Rashid, Khalid, Verhoyen, Mathilde, Taiwo, Moyinoluwa and Langmann, Thomas (2020). Translocator protein (18 kDa) (TSPO) ligands activate Nrf2 signaling and attenuate inflammatory responses and oxidative stress in human retinal pigment epithelial cells. Biochem. Biophys. Res. Commun., 528 (2). S. 261 - 269. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE. ISSN 1090-2104

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Abstract

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. (C) 2020 The Authors. Published by Elsevier Inc.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rashid, Khalid UNSPECIFIED UNSPECIFIED UNSPECIFIED Verhoyen, Mathilde UNSPECIFIED UNSPECIFIED UNSPECIFIED Taiwo, Moyinoluwa UNSPECIFIED UNSPECIFIED UNSPECIFIED Langmann, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-325855
DOI:	10.1016/j.bbrc.2020.05.114
Journal or Publication Title:	Biochem. Biophys. Res. Commun.
Volume:	528
Number:	2
Page Range:	S. 261 - 269
Date:	2020
Publisher:	ACADEMIC PRESS INC ELSEVIER SCIENCE
Place of Publication:	SAN DIEGO
ISSN:	1090-2104
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LYSOSOMAL DESTABILIZATION; MOUSE MODEL; RPE; DEGENERATION; OXYGENASE-1; MICROGLIA; TARGET; HEME Multiple languages Biochemistry & Molecular Biology; Biophysics Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/32585