The unfolding web of innate immune dysregulation in alcoholic liver injury
Open accessAbstract
Inflammatory cell and cytokine cascade activation is present in humans with alcoholic liver disease as well as in animal models of alcohol-induced liver damage. Gut-derived lipopolysaccharide (LPS), a ligand of the Toll-like receptor 4 (TLR4), plays a central role in triggering and maintaining activation of Kupffer cells in alcoholic hepatitis. In this mini-review, we describe molecular mechanisms that lead to increased inflammatory cell activation by alcohol and LPS and discuss the mechanism for activation in alcohol-exposed macrophages. In alcohol-induced liver disease we discuss the role of MyD88-independent but IRF3-mediated TLR4 signaling in alcohol-related liver inflammation and liver damage.
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Alcoholic liver disease involves inflammation, in part through an alcohol-induced increase in gut permeability to endotoxins such as lipopolysaccharide that activate innate immune cells in the liver.
“Alcoholic liver disease involves inflammation, in part through an alcohol-induced increase in the permeability of the gut to endotoxins, such as lipopolysaccharide, that activate innate immune cells in the liver (Szabo et al., 2011).”
From Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development (2021) · cites this paper as Szabo et al., 2011
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- Authors
- Szabo, G., Mandrekar, P., Petrasek, J., & Catalano, D.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- Venue
- Alcoholism: Clinical and Experimental Research
- Publisher
- Wiley
- Published
- 2011-02-01
- Volume
- 35
- Issue
- 5
- Pages
- 782-786
- ISSN
- 0145-6008 (ISSN-L)
- PMC
- PMC3742381
- OpenAlex
- W1563860173
- Cited by
- 82
- References
- 39
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 10 · 2018: 4 · 2017: 6 · 2016: 8 · 2015: 8 · 2014: 6 · 2013: 14 · 2012: 7
- FWCI
- 1.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alcoholism Clinical and Experimental Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (R01AA017729, R21AA017545, AA017729, #AA011576, R01AA011576, R01AA017986)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- alcoholic liver disease, alcoholic hepatitis, innate immunity, lipopolysaccharide, TLR4, Kupffer cells, macrophages, MyD88-independent signaling, IRF3 signaling, cytokine cascade, gut-liver axis, liver inflammation
- MeSH terms
- Alcoholism, Animals, Humans, Immunity, Innate, Liver, Liver Diseases, Alcoholic, Gastrointestinal Tract, Toll-Like Receptor 4
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