ArticleHepatology (Baltimore, Md.)2008
Ethanol and arachidonic acid synergize to activate Kupffer cells and modulate the fibrogenic response via tumor necrosis factor alpha, reduced glutathione, and transforming growth factor beta-dependent mechanisms.
Article in Hepatology (Baltimore, Md.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 58 citations in OpenAlex.
- A combination of ethanol and arachidonic acid promotes steatosis and endoplasmic reticulum stress and impairs mitochondrial respiration in H9c2 cardiomyoblasts.Lipids in health and disease · 2025Article
- Redox-sensitive high-mobility group box-1 isoforms contribute to liver fibrosis progression and resolution in mice.Journal of hepatology · 2024Article
- Role of hepatic stellate cells in liver ischemia-reperfusion injury.Frontiers in immunology · 2022Review
- Kweichow Moutai ameliorates alcohol-induced liver fibrosis in mice by targeting the NFκB pathway.Food science & nutrition · 2020Article
- Alcoholic liver disease: Utility of animal models.World journal of gastroenterology · 2018Review
- Cartilage oligomeric matrix protein participates in the pathogenesis of liver fibrosis.Journal of hepatology · 2016Article
- Sinusoidal communication in liver fibrosis and regeneration.Journal of hepatology · 2016Review
- Hepatic non-parenchymal cells: Master regulators of alcoholic liver disease?World journal of gastroenterology · 2016Review
- Virological Mechanisms in the Coinfection between HIV and HCV.Mediators of inflammation · 2015Review
- NADPH Oxidases in Chronic Liver Diseases.Advances in hepatology · 2014Article
- Extracellular matrix and liver disease.Antioxidants & redox signaling · 2014Review
- Peroxisome proliferator-activated receptor α, a potential therapeutic target for alcoholic liver disease.World journal of gastroenterology · 2014Review
- HIV-1 Nef is transferred from expressing T cells to hepatocytic cells through conduits and enhances HCV replication.PloS one · 2014Article
- Genome-wide transcriptome analysis identifies novel gene signatures implicated in human chronic liver disease.American journal of physiology. Gastrointestinal and liver physiology · 2013Article
- Milk osteopontin, a nutritional approach to prevent alcohol-induced liver injury.American journal of physiology. Gastrointestinal and liver physiology · 2013Article
- CD14 upregulation as a distinct feature of non-alcoholic fatty liver disease after pancreatoduodenectomy.World journal of hepatology · 2013Article
- Activation of peroxisome proliferator activated receptor alpha ameliorates ethanol mediated liver fibrosis in mice.Lipids in health and disease · 2013Article
- Inflammation in alcoholic liver disease.Annual review of nutrition · 2012Review
- Arachidonic acid stimulates TNFα production in Kupffer cells via a reactive oxygen species-pERK1/2-Egr1-dependent mechanism.American journal of physiology. Gastrointestinal and liver physiology · 2012Article
- Fibromodulin, an oxidative stress-sensitive proteoglycan, regulates the fibrogenic response to liver injury in mice.Gastroenterology · 2012Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledBecause of the contribution of ethanol and polyunsaturated fatty acids (PUFAs) to alcoholic liver disease, we investigated whether chronic ethanol administration and arachidonic acid (AA) could synergistically mediate Kupffer cell (KC) activation and modulate the stellate cell (HSC) fibrogenic response.
results(1) the effects of ethanol and AA on KC and HSC were as follows: Cell proliferation, lipid peroxidation, H(2)O(2), O(2).(-), nicotinamide adenine dinucleotide phosphate reduced form (NADPH) oxidase activity, and tumor necrosis factor alpha (TNF-alpha) were higher in KC(ethanol) than in KC(control), and were enhanced by AA; HSC(ethanol) proliferated faster, increased collagen, and showed higher GSH than HSC(control), with modest effects by AA. (2) AA effects on the control co-culture: We previously reported the ability of KC to induce a pro-fibrogenic response in HSC via reactive oxygen species (ROS)-dependent mechanisms; we now show that AA further increases cell proliferation and collagen in the control co-culture. The latter was prevented by vitamin E (an antioxidant) and by diphenyleneiodonium (a NADPH oxidase inhibitor). (3) Ethanol effects on the co-cultures: Co-culture with KC(control) or KC(ethanol) induced HSC(control) and HSC(ethanol) proliferation; however, the pro-fibrogenic response in HSC(ethanol) was suppressed because of up-regulation of TNF-alpha and GSH, which was prevented by a TNF-alpha neutralizing antibody (Ab) and by L-buthionine-sulfoximine, a GSH-depleting agent. (4) Ethanol plus AA effects on the co-cultures: AA lowered TNF-alpha in the HSC(control) co-cultures, allowing for enhanced collagen deposition; furthermore, AA restored the pro-fibrogenic response in the HSC(ethanol) co-cultures by counteracting the up-regulation of TNF-alpha and GSH with a significant increase in GSSG and in pro-fibrogenic transforming growth factor beta (TGF-beta).
conclusionThese results unveil synergism between ethanol and AA to the mechanism whereby KC mediate ECM remodeling and suggest that even if chronic ethanol consumption sensitizes HSC to up-regulate anti-fibrogenic signals, their effects are blunted by a second "hit" such as AA.
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