期刊
JOURNAL OF HEPATOLOGY
卷 59, 期 3, 页码 583-594出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jhep.2013.03.033
关键词
Apoptosis; Lipotoxicity; Necrosis; Non-alcoholic necrosis steatohepatitis; Pattern recognition receptors; Tumor necrosis factor receptor
资金
- Agence National de la Recherche (ANR) [ANR-10-LABX-33]
- European Commission (ArtForce)
- ANR
- Ligue contre le Cancer (Equipe labellisee)
- Fondation pour la Recherche Medicale (FRM)
- Institut National du Cancer (INCa)
- LabEx Immuno-Oncologie
- Fondation de France
- Fondation Bettencourt-Schueller
- AXA Chair for Longevity Research
- Canceropole Ile-de-France
- Paris Alliance of Cancer Research Institutes (PACRI)
- Cancer Research for Personalized Medicine (CARPEM)
Inflammation can be either beneficial or detrimental to the liver, depending on multiple factors. Mild (i.e., limited in intensity and destined to resolve) inflammatory responses have indeed been shown to exert consistent hepatoprotective effects, contributing to tissue repair and promoting the re-establishment of homeostasis. Conversely, excessive (i.e., disproportionate in intensity and permanent) inflammation may induce a massive loss of hepatocytes and hence exacerbate the severity of various hepatic conditions, including ischemia-reperfusion injury, systemic metabolic alterations (e. g., obesity, diabetes, non-alcoholic fatty liver disorders), alcoholic hepatitis, intoxication by xenobiotics and infection, de facto being associated with irreversible liver damage, fibrosis, and carcinogenesis. Both liver-resident cells (e. g., Kupffer cells, hepatic stellate cells, sinusoidal endothelial cells) and cells that are recruited in response to injury (e. g., monocytes, macrophages, dendritic cells, natural killer cells) emit pro-inflammatory signals including - but not limited to - cytokines, chemokines, lipid messengers, and reactive oxygen species that contribute to the apoptotic or necrotic demise of hepatocytes. In turn, dying hepatocytes release damage-associated molecular patterns that-upon binding to evolutionary conserved pattern recognition receptors-activate cells of the innate immune system to further stimulate inflammatory responses, hence establishing a highly hepatotoxic feedforward cycle of inflammation and cell death. In this review, we discuss the cellular and molecular mechanisms that account for the most deleterious effect of hepatic inflammation at the cellular level, that is, the initiation of a massive cell death response among hepatocytes. (C) 2013 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.
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