Anti-Inflammatory and Anti-Oxidative Effects of AM404 in IL-1β-Stimulated SK-N-SH Neuroblastoma Cells

An emerging number of studies address the involvement of neuroinflammation and oxidative stress in the pathophysiology of central nervous system (CNS) disorders such as depression, schizophrenia, anxiety, and neurodegenerative diseases. Different cytokines and molecules, such as prostaglandin (PG) E...

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Autores principales:	Matthias Apweiler, Jana Streyczek, Soraya Wilke Saliba, Johannes Ditrich, Eduardo Muñoz, Bernd L. Fiebich
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	AM404 paracetamol acetaminophen prostaglandin E2 8-iso-PGF2α cyclooxygenase Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/c9bb7d6e820b471e895d33cdf71c8dc0
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spelling	oai:doaj.org-article:c9bb7d6e820b471e895d33cdf71c8dc02021-11-17T06:17:04ZAnti-Inflammatory and Anti-Oxidative Effects of AM404 in IL-1β-Stimulated SK-N-SH Neuroblastoma Cells1663-981210.3389/fphar.2021.789074https://doaj.org/article/c9bb7d6e820b471e895d33cdf71c8dc02021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.789074/fullhttps://doaj.org/toc/1663-9812An emerging number of studies address the involvement of neuroinflammation and oxidative stress in the pathophysiology of central nervous system (CNS) disorders such as depression, schizophrenia, anxiety, and neurodegenerative diseases. Different cytokines and molecules, such as prostaglandin (PG) E2, are associated with neuroinflammatory processes. The active acetaminophen metabolite AM404 has been shown to prevent inflammation and neuroinflammation in primary microglia and organotypic hippocampal slice cultures. However, its effects on pathophysiological conditions in the CNS and especially on neurons are still poorly understood. In this study, we therefore evaluated the effects of AM404 and acetaminophen on the arachidonic acid cascade and oxidative stress induced by interleukin (IL)-1β in human SK-N-SH neuronal cells. We observed that AM404 and acetaminophen significantly and concentration-dependent inhibited IL-1β-induced release of PGE2, independent of cyclooxygenases (COX)-1 and COX-2 enzymatic activity as well as COX-2 mRNA and protein levels in SK-N-SH-cells. The reduction of IL-1β-induced PGE2-release by AM404 and acetaminophen treatment might be mediated by the 8-iso-PGF2α pathway since IL-1β-induced synthesis of this free radical marker is dose-dependently reduced by both compounds, respectively. Therefore, understanding of the potential therapeutic properties of AM404 in neuroinflammation and oxidative stress might lead to future treatment options of different neurological disorders.Matthias ApweilerJana StreyczekSoraya Wilke SalibaJohannes DitrichEduardo MuñozEduardo MuñozEduardo MuñozBernd L. FiebichFrontiers Media S.A.articleAM404paracetamolacetaminophenprostaglandin E28-iso-PGF2αcyclooxygenaseTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	AM404 paracetamol acetaminophen prostaglandin E2 8-iso-PGF2α cyclooxygenase Therapeutics. Pharmacology RM1-950
spellingShingle	AM404 paracetamol acetaminophen prostaglandin E2 8-iso-PGF2α cyclooxygenase Therapeutics. Pharmacology RM1-950 Matthias Apweiler Jana Streyczek Soraya Wilke Saliba Johannes Ditrich Eduardo Muñoz Eduardo Muñoz Eduardo Muñoz Bernd L. Fiebich Anti-Inflammatory and Anti-Oxidative Effects of AM404 in IL-1β-Stimulated SK-N-SH Neuroblastoma Cells
description	An emerging number of studies address the involvement of neuroinflammation and oxidative stress in the pathophysiology of central nervous system (CNS) disorders such as depression, schizophrenia, anxiety, and neurodegenerative diseases. Different cytokines and molecules, such as prostaglandin (PG) E2, are associated with neuroinflammatory processes. The active acetaminophen metabolite AM404 has been shown to prevent inflammation and neuroinflammation in primary microglia and organotypic hippocampal slice cultures. However, its effects on pathophysiological conditions in the CNS and especially on neurons are still poorly understood. In this study, we therefore evaluated the effects of AM404 and acetaminophen on the arachidonic acid cascade and oxidative stress induced by interleukin (IL)-1β in human SK-N-SH neuronal cells. We observed that AM404 and acetaminophen significantly and concentration-dependent inhibited IL-1β-induced release of PGE2, independent of cyclooxygenases (COX)-1 and COX-2 enzymatic activity as well as COX-2 mRNA and protein levels in SK-N-SH-cells. The reduction of IL-1β-induced PGE2-release by AM404 and acetaminophen treatment might be mediated by the 8-iso-PGF2α pathway since IL-1β-induced synthesis of this free radical marker is dose-dependently reduced by both compounds, respectively. Therefore, understanding of the potential therapeutic properties of AM404 in neuroinflammation and oxidative stress might lead to future treatment options of different neurological disorders.
format	article
author	Matthias Apweiler Jana Streyczek Soraya Wilke Saliba Johannes Ditrich Eduardo Muñoz Eduardo Muñoz Eduardo Muñoz Bernd L. Fiebich
author_facet	Matthias Apweiler Jana Streyczek Soraya Wilke Saliba Johannes Ditrich Eduardo Muñoz Eduardo Muñoz Eduardo Muñoz Bernd L. Fiebich
author_sort	Matthias Apweiler
title	Anti-Inflammatory and Anti-Oxidative Effects of AM404 in IL-1β-Stimulated SK-N-SH Neuroblastoma Cells
title_short	Anti-Inflammatory and Anti-Oxidative Effects of AM404 in IL-1β-Stimulated SK-N-SH Neuroblastoma Cells
title_full	Anti-Inflammatory and Anti-Oxidative Effects of AM404 in IL-1β-Stimulated SK-N-SH Neuroblastoma Cells
title_fullStr	Anti-Inflammatory and Anti-Oxidative Effects of AM404 in IL-1β-Stimulated SK-N-SH Neuroblastoma Cells
title_full_unstemmed	Anti-Inflammatory and Anti-Oxidative Effects of AM404 in IL-1β-Stimulated SK-N-SH Neuroblastoma Cells
title_sort	anti-inflammatory and anti-oxidative effects of am404 in il-1β-stimulated sk-n-sh neuroblastoma cells
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/c9bb7d6e820b471e895d33cdf71c8dc0
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Anti-Inflammatory and Anti-Oxidative Effects of AM404 in IL-1β-Stimulated SK-N-SH Neuroblastoma Cells

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