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Macrophage pathology in hepatotoxicity

The liver is the most important organ that metabolizes and detoxifies chemicals taken into the body. Therefore, there is always a risk of liver damage owing to the toxic effects of chemicals. The mechanisms of hepatotoxicity have been studied extensively and deeply based on toxic effects of chemical...

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Autores principales: Yamate, Jyoji, Izawa, Takeshi, Kuwamura, Mitsuru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Japanese Society of Toxicologic Pathology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10123298/
https://www.ncbi.nlm.nih.gov/pubmed/37101958
http://dx.doi.org/10.1293/tox.2022-0112
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author Yamate, Jyoji
Izawa, Takeshi
Kuwamura, Mitsuru
author_facet Yamate, Jyoji
Izawa, Takeshi
Kuwamura, Mitsuru
author_sort Yamate, Jyoji
collection PubMed
description The liver is the most important organ that metabolizes and detoxifies chemicals taken into the body. Therefore, there is always a risk of liver damage owing to the toxic effects of chemicals. The mechanisms of hepatotoxicity have been studied extensively and deeply based on toxic effects of chemicals themselves. However, it is important to note that liver damage is variously modified by the patho-biological reactions evoked mainly via macrophages. Macrophages appearing in hepatotoxicity are evaluated by the M1/M2 polarization; M1 macrophages promote tissue injury/inflammation, whereas M2 macrophages show anti-inflammatory action including reparative fibrosis. The “portal vein-liver barrier” regulated by Kupffer cells and dendritic cells in and around the Glisson’s sheath may be related to the initiation of hepatotoxicity. In addition, Kupffer cells exhibit the two-sides of functions (that is, M1 or M2 macrophage-like functions), depending on microenvironmental conditions which may be raised in part by gut microbiota-derived lipopolysaccharide. Furthermore, damage-associated molecular patterns (DAMPs) (in particular, HMGB1) and autophagy (which degrades DAMPs) also play roles in the polarity of M1/M2 macrophages. The mutual relation of “DAMPs (HMGB-1)–autophagy–M1/M2 macrophage polarization” as the patho-biological reaction should be taken into consideration in hepatotoxicity evaluation.
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spelling pubmed-101232982023-04-25 Macrophage pathology in hepatotoxicity Yamate, Jyoji Izawa, Takeshi Kuwamura, Mitsuru J Toxicol Pathol Invited Review The liver is the most important organ that metabolizes and detoxifies chemicals taken into the body. Therefore, there is always a risk of liver damage owing to the toxic effects of chemicals. The mechanisms of hepatotoxicity have been studied extensively and deeply based on toxic effects of chemicals themselves. However, it is important to note that liver damage is variously modified by the patho-biological reactions evoked mainly via macrophages. Macrophages appearing in hepatotoxicity are evaluated by the M1/M2 polarization; M1 macrophages promote tissue injury/inflammation, whereas M2 macrophages show anti-inflammatory action including reparative fibrosis. The “portal vein-liver barrier” regulated by Kupffer cells and dendritic cells in and around the Glisson’s sheath may be related to the initiation of hepatotoxicity. In addition, Kupffer cells exhibit the two-sides of functions (that is, M1 or M2 macrophage-like functions), depending on microenvironmental conditions which may be raised in part by gut microbiota-derived lipopolysaccharide. Furthermore, damage-associated molecular patterns (DAMPs) (in particular, HMGB1) and autophagy (which degrades DAMPs) also play roles in the polarity of M1/M2 macrophages. The mutual relation of “DAMPs (HMGB-1)–autophagy–M1/M2 macrophage polarization” as the patho-biological reaction should be taken into consideration in hepatotoxicity evaluation. Japanese Society of Toxicologic Pathology 2022-11-29 2023-04 /pmc/articles/PMC10123298/ /pubmed/37101958 http://dx.doi.org/10.1293/tox.2022-0112 Text en ©2023 The Japanese Society of Toxicologic Pathology https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. (CC-BY-NC-ND 4.0: https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Invited Review
Yamate, Jyoji
Izawa, Takeshi
Kuwamura, Mitsuru
Macrophage pathology in hepatotoxicity
title Macrophage pathology in hepatotoxicity
title_full Macrophage pathology in hepatotoxicity
title_fullStr Macrophage pathology in hepatotoxicity
title_full_unstemmed Macrophage pathology in hepatotoxicity
title_short Macrophage pathology in hepatotoxicity
title_sort macrophage pathology in hepatotoxicity
topic Invited Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10123298/
https://www.ncbi.nlm.nih.gov/pubmed/37101958
http://dx.doi.org/10.1293/tox.2022-0112
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