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Hesperetin, a Citrus Flavonoid, Ameliorates Inflammatory Cytokine-Mediated Inhibition of Oligodendroglial Cell Morphological Differentiation

Oligodendrocytes (oligodendroglial cells) are glial cells that wrap neuronal axons with their differentiated plasma membranes called myelin membranes. In the pathogenesis of inflammatory cytokine-related oligodendroglial cell and myelin diseases such as multiple sclerosis (MS), typical inflammatory...

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Autores principales: Nishino, Satoshi, Fujiki, Yoko, Sato, Takanari, Kato, Yukino, Shirai, Remina, Oizumi, Hiroaki, Yamamoto, Masahiro, Ohbuchi, Katsuya, Miyamoto, Yuki, Mizoguchi, Kazushige, Yamauchi, Junji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9230394/
https://www.ncbi.nlm.nih.gov/pubmed/35736620
http://dx.doi.org/10.3390/neurolint14020039
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author Nishino, Satoshi
Fujiki, Yoko
Sato, Takanari
Kato, Yukino
Shirai, Remina
Oizumi, Hiroaki
Yamamoto, Masahiro
Ohbuchi, Katsuya
Miyamoto, Yuki
Mizoguchi, Kazushige
Yamauchi, Junji
author_facet Nishino, Satoshi
Fujiki, Yoko
Sato, Takanari
Kato, Yukino
Shirai, Remina
Oizumi, Hiroaki
Yamamoto, Masahiro
Ohbuchi, Katsuya
Miyamoto, Yuki
Mizoguchi, Kazushige
Yamauchi, Junji
author_sort Nishino, Satoshi
collection PubMed
description Oligodendrocytes (oligodendroglial cells) are glial cells that wrap neuronal axons with their differentiated plasma membranes called myelin membranes. In the pathogenesis of inflammatory cytokine-related oligodendroglial cell and myelin diseases such as multiple sclerosis (MS), typical inflammatory cytokines tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) are thought to contribute to the degeneration and/or progression of the degeneration of oligodendroglial cells and, in turn, the degeneration of naked neuronal cells in the central nervous system (CNS) tissues. Despite the known involvement of these inflammatory cytokines in disease progression, it has remained unclear whether and how TNFα or IL-6 affects the oligodendroglial cells themselves or indirectly. Here we show that TNFα or IL-6 directly inhibits morphological differentiation in FBD-102b cells, which are differentiation models of oligodendroglial cells. Their phenotype changes were supported by the decreased expression levels of oligodendroglial cell differentiation and myelin marker proteins. In addition, TNFα or IL-6 decreased phosphorylation levels of Akt kinase, whose upregulation has been associated with promoting oligodendroglial cell differentiation. Hesperetin, a flavonoid mainly contained in citrus fruit, is known to have neuroprotective effects. Hesperetin might also be able to resolve pre-illness conditions, including the irregulated secretion of cytokines, through diet. Notably, the addition of hesperetin into cells recovered TNFα- or IL-6-induced inhibition of differentiation, as supported by increased levels of marker protein expression and phosphorylation of Akt kinase. These results suggest that TNFα or IL-6 itself contributes to the inhibitory effects on the morphological differentiation of oligodendroglial cells, possibly providing information not only on their underlying pathological effects but also on flavonoids with potential therapeutic effects at the molecular and cellular levels.
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spelling pubmed-92303942022-06-25 Hesperetin, a Citrus Flavonoid, Ameliorates Inflammatory Cytokine-Mediated Inhibition of Oligodendroglial Cell Morphological Differentiation Nishino, Satoshi Fujiki, Yoko Sato, Takanari Kato, Yukino Shirai, Remina Oizumi, Hiroaki Yamamoto, Masahiro Ohbuchi, Katsuya Miyamoto, Yuki Mizoguchi, Kazushige Yamauchi, Junji Neurol Int Article Oligodendrocytes (oligodendroglial cells) are glial cells that wrap neuronal axons with their differentiated plasma membranes called myelin membranes. In the pathogenesis of inflammatory cytokine-related oligodendroglial cell and myelin diseases such as multiple sclerosis (MS), typical inflammatory cytokines tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) are thought to contribute to the degeneration and/or progression of the degeneration of oligodendroglial cells and, in turn, the degeneration of naked neuronal cells in the central nervous system (CNS) tissues. Despite the known involvement of these inflammatory cytokines in disease progression, it has remained unclear whether and how TNFα or IL-6 affects the oligodendroglial cells themselves or indirectly. Here we show that TNFα or IL-6 directly inhibits morphological differentiation in FBD-102b cells, which are differentiation models of oligodendroglial cells. Their phenotype changes were supported by the decreased expression levels of oligodendroglial cell differentiation and myelin marker proteins. In addition, TNFα or IL-6 decreased phosphorylation levels of Akt kinase, whose upregulation has been associated with promoting oligodendroglial cell differentiation. Hesperetin, a flavonoid mainly contained in citrus fruit, is known to have neuroprotective effects. Hesperetin might also be able to resolve pre-illness conditions, including the irregulated secretion of cytokines, through diet. Notably, the addition of hesperetin into cells recovered TNFα- or IL-6-induced inhibition of differentiation, as supported by increased levels of marker protein expression and phosphorylation of Akt kinase. These results suggest that TNFα or IL-6 itself contributes to the inhibitory effects on the morphological differentiation of oligodendroglial cells, possibly providing information not only on their underlying pathological effects but also on flavonoids with potential therapeutic effects at the molecular and cellular levels. MDPI 2022-05-31 /pmc/articles/PMC9230394/ /pubmed/35736620 http://dx.doi.org/10.3390/neurolint14020039 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nishino, Satoshi
Fujiki, Yoko
Sato, Takanari
Kato, Yukino
Shirai, Remina
Oizumi, Hiroaki
Yamamoto, Masahiro
Ohbuchi, Katsuya
Miyamoto, Yuki
Mizoguchi, Kazushige
Yamauchi, Junji
Hesperetin, a Citrus Flavonoid, Ameliorates Inflammatory Cytokine-Mediated Inhibition of Oligodendroglial Cell Morphological Differentiation
title Hesperetin, a Citrus Flavonoid, Ameliorates Inflammatory Cytokine-Mediated Inhibition of Oligodendroglial Cell Morphological Differentiation
title_full Hesperetin, a Citrus Flavonoid, Ameliorates Inflammatory Cytokine-Mediated Inhibition of Oligodendroglial Cell Morphological Differentiation
title_fullStr Hesperetin, a Citrus Flavonoid, Ameliorates Inflammatory Cytokine-Mediated Inhibition of Oligodendroglial Cell Morphological Differentiation
title_full_unstemmed Hesperetin, a Citrus Flavonoid, Ameliorates Inflammatory Cytokine-Mediated Inhibition of Oligodendroglial Cell Morphological Differentiation
title_short Hesperetin, a Citrus Flavonoid, Ameliorates Inflammatory Cytokine-Mediated Inhibition of Oligodendroglial Cell Morphological Differentiation
title_sort hesperetin, a citrus flavonoid, ameliorates inflammatory cytokine-mediated inhibition of oligodendroglial cell morphological differentiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9230394/
https://www.ncbi.nlm.nih.gov/pubmed/35736620
http://dx.doi.org/10.3390/neurolint14020039
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