ArticleHepatology (Baltimore, Md.)2009
An early complement-dependent and TLR-4-independent phase in the pathogenesis of ethanol-induced liver injury in mice.
Article in Hepatology (Baltimore, Md.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
72 citing papers in PubMed, 101 citations in OpenAlex.
- tRNA‑derived RNAs in hepatic diseases: From biological functions to clinical translation (Review).International journal of molecular medicine · 2026Review
- Liver Macrophage Changes during Early Adaptation to Alcohol Exposure.The American journal of pathology · 2026Article
- Ethanol causes rapid decreases in the hepatic retinoid levels shaping the early steps of alcohol-associated liver disease.Alcohol, clinical & experimental research · 2025Article
- Role of Complement in Liver Diseases.Seminars in liver disease · 2024Review
- Hyaluronan synthesis inhibition normalizes ethanol-enhanced hepatic stellate cell activation.Alcohol, clinical & experimental research · 2023Article
- The sirtuin family in health and disease.Signal transduction and targeted therapy · 2022Review
- Hepatic CYP2B10 is highly induced by binge ethanol and contributes to acute-on-chronic alcohol-induced liver injury.Alcoholism, clinical and experimental research · 2022Article
- A Dual Role of Complement Activation in the Development of Fulminant Hepatic Failure Induced by Murine-Beta-Coronavirus Infection.Frontiers in cellular and infection microbiology · 2022Article
- Liver regeneration and inflammation: from fundamental science to clinical applications.Nature reviews. Molecular cell biology · 2021Review
- The Purinergic P2X7 Receptor-NLRP3 Inflammasome Pathway: A New Target in Alcoholic Liver Disease?International journal of molecular sciences · 2021Review
- Roles of the complement system in alcohol-induced liver disease.Clinical and molecular hepatology · 2020Review
- Alcohol-induced adipose tissue macrophage phenotypic switching is independent of myeloid Toll-like receptor 4 expression.American journal of physiology. Cell physiology · 2019Article
- Complement C3 activation regulates the production of tRNA-derived fragments Gly-tRFs and promotes alcohol-induced liver injury and steatosis.Cell research · 2019Article
- Phagocytosis of Necrotic Debris at Sites of Injury and Inflammation.Frontiers in immunology · 2019Review
- FOXO3-dependent apoptosis limits alcohol-induced liver inflammation by promoting infiltrating macrophage differentiation.Cell death discovery · 2018Article
- Complements are involved in alcoholic fatty liver disease, hepatitis and fibrosis.World journal of hepatology · 2018Review
- Complement Factor D protects mice from ethanol-induced inflammation and liver injury.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Article
- Review
- Targeting inflammation for the treatment of alcoholic liver disease.Pharmacology & therapeutics · 2017Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
unlabelledThe innate immune system has been implicated in the pathogenesis of alcoholic liver disease. Although innate immunity is usually considered an early response to injury, previous work implicating innate immunity in ethanol-induced liver injury focuses primarily on long-term ethanol exposure. We investigated the early period of ethanol exposure to determine whether there were temporal associations between activation of innate immune responses and known correlates of liver injury. Female C57BL/6 mice were allowed free access to an ethanol-containing Lieber-DeCarli diet or were pair-fed a control diet. Within 4 days of ethanol exposure, we observed a striking spike in expression of hepatic proinflammatory cytokines-including tumor necrosis factor alpha (TNF-alpha), interleukin-6, and interferon-gamma-prior to hepatic triglyceride accumulation or increased plasma alanine aminotransferase activities, as well as before the induction of cytochrome P450 2E1 or oxidative stress. This early spike in inflammatory cytokines coincided with deposition of C3b-iC3b/C3c (C3b) in the liver. This deposition, resulting from the cleavage of the third component of the complement system (C3), is evidence for activation of complement in response to ethanol. C3(-/-) mice were protected from the early, ethanol-induced increase in hepatic TNF-alpha expression. Ethanol increased C3b deposition in mice deficient in C3a receptor or C5a receptor, as well as in wild-type mice depleted of hepatic macrophages; however, there was no increase in hepatic TNF-alpha in the absence of C3a receptor, C5a receptor, or hepatic macrophages. In contrast, the absence of Toll-like receptor 4 (TLR-4) had no effect on the early, ethanol-induced increase in either C3b or TNF-alpha.
conclusionWe have identified a complement- and macrophage-dependent, but TLR-4 independent, phase in the pathogenesis of ethanol-induced liver injury.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.