Universität zu Köln

Khan, Amir Saeed, Wolf, Anne ORCID: 0000-0003-2551-9821 and Langmann, Thomas (2021). The AhR ligand 2, 2 '-aminophenyl indole (2AI) regulates microglia homeostasis and reduces pro-inflammatory signaling. Biochem. Biophys. Res. Commun., 579. S. 15 - 22. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE. ISSN 1090-2104

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Abstract

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. (C) 2021 The Authors. Published by Elsevier Inc.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Khan, Amir Saeed UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolf, Anne UNSPECIFIED orcid.org/0000-0003-2551-9821 UNSPECIFIED Langmann, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-574786
DOI:	10.1016/j.bbrc.2021.09.054
Journal or Publication Title:	Biochem. Biophys. Res. Commun.
Volume:	579
Page Range:	S. 15 - 22
Date:	2021
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 ARYL-HYDROCARBON RECEPTOR; TARGET Multiple languages Biochemistry & Molecular Biology; Biophysics Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57478