ArticleJournal of immunology (Baltimore, Md. : 1950)2009
Ethanol augments RANTES/CCL5 expression in rat liver sinusoidal endothelial cells and human endothelial cells via activation of NF-kappa B, HIF-1 alpha, and AP-1.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 57 citations in OpenAlex.
- Integrated Network and Transcriptomic Analyses Identify a Candidate Ethanol-ADAM17 Molecular Axis Associated with Glioblastoma Progression.International journal of molecular sciences · 2026Article
- HMGB1-mediated enhancement of glycolysis activates hepatic stellate cells by inhibiting ferroptosis in alcoholic hepatic fibrosis.Stem cell research & therapy · 2026Article
- Exercise-induced changes in circulatory aging-related biomarkers among older adults: longitudinal analysis of a multi-stage randomized clinical trial.Immunity & ageing : I & A · 2026Article
- Immunological mechanisms and emerging therapeutic targets in alcohol-associated liver disease.Cellular & molecular immunology · 2025Review
- Decreased antioxidant-related superoxide dismutase 1 expression in peripheral immune cells indicates early ethanol exposure.Scientific reports · 2024Article
- GET73 modulates lipopolysaccharide- and ethanol-induced increase in cytokine/chemokine levels in primary cultures of microglia of rat cerebral cortex.Pharmacological reports : PR · 2024Article
- Signal Transduction and Gene Regulation in the Endothelium.Cold Spring Harbor perspectives in medicine · 2023Review
- Immune-regulating strategy against rheumatoid arthritis by inducing tolerogenic dendritic cells with modified zinc peroxide nanoparticles.Journal of nanobiotechnology · 2022Article
- Dietary camellia seed oil attenuates liver injury in mice chronically exposed to alcohol.Frontiers in nutrition · 2022Article
- Alcohol induces mitochondrial derangements in alveolar macrophages by upregulating NADPH oxidase 4.Alcohol (Fayetteville, N.Y.) · 2021Article
- Protein kinase Ds promote tumor angiogenesis through mast cell recruitment and expression of angiogenic factors in prostate cancer microenvironment.Journal of experimental & clinical cancer research : CR · 2019Article
- Role of Alcohol Oxidative Metabolism in Its Cardiovascular and Autonomic Effects.Advances in experimental medicine and biology · 2019Review
- Role of HIF-1α in Alcohol-Mediated Multiple Organ Dysfunction.Biomolecules · 2018Review
- Abnormal expression of TFIIIB subunits and RNA Pol III genes is associated with hepatocellular carcinoma.Liver research (Beijing, China) · 2017Article
- Alcohol and inflammatory responses: Highlights of the 2015 Alcohol and Immunology Research Interest Group (AIRIG) meeting.Alcohol (Fayetteville, N.Y.) · 2016Article
- Peroxisome Proliferator-Activated Receptor γ Regulates Chronic Alcohol-Induced Alveolar Macrophage Dysfunction.American journal of respiratory cell and molecular biology · 2016Article
- Role of Transcription Factors in Steatohepatitis and Hypertension after Ethanol: The Epicenter of Metabolism.Biomolecules · 2016Review
- Short Term Hypoxia Synergizes with Interleukin 15 Priming in Driving Glycolytic Gene Transcription and Supports Human Natural Killer Cell Activities.The Journal of biological chemistry · 2016Article
- A new HIF-1α/RANTES-driven pathway to hepatocellular carcinoma mediated by germline haploinsufficiency of SART1/HAF in mice.Hepatology (Baltimore, Md.) · 2016Article
- Migration of bone marrow progenitor cells in the adult brain of rats and rabbits.World journal of stem cells · 2016Review
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Chronic alcohol consumption leads to liver inflammation and cirrhosis. Alcoholic liver disease patients have increased levels of hepatic RANTES/CCL5. However, less is known about the molecular mechanisms for ethanol-induced RANTES up-regulation. In this study, we observed that liver sinusoidal endothelial cells derived from ethanol-fed rats (E-rLSECs) showed severalfold increases in RANTES and hypoxia-inducible factor 1alpha (HIF-1alpha) mRNAs compared with control rLSECs (C-rLSECs). Similar effects were seen in acute ethanol treatment of isolated rLSECs and human dermal microvascular endothelial cells. Ethanol-induced RANTES mRNA expression required ethanol metabolism, p38 MAPK, HIF-1alpha, and JNK-2, but not JNK-1. EMSA experiments showed increased HIF-1alpha binding to wild-type hypoxia response elements (HREs; -31 to -9 bp) within the RANTES promoter in response to ethanol. RANTES promoter analysis showed that cis elements proximal to the transcription start site, HRE-1 (nt -22 to -19), HRE-2 (nt -32 to -29), and AP-1 (nt -250 to -244) were required for ethanol-mediated RANTES expression. These results were corroborated by chromatin immunoprecipitation assays showing augmented HIF-1alpha binding to HRE-1. Additionally, promoter analysis revealed c-Jun, c-Jun/c-Fos, and JunD, but not JunB, bound to the AP-1 site of the RANTES promoter. Ethanol-mediated activation of NF-kappaB led to HIF-1alpha activation and concomitant RANTES expression. Plasma of ethanol-fed c-Jun(flox/flox)-Mx-1-Cre mice showed attenuated levels of RANTES compared with ethanol-fed control mice, supporting the role of c-Jun in ethanol-induced RANTES expression. Our studies showed that ethanol-mediated RANTES/CCL5 expression occurs via HIF-1alpha activation independently of hypoxia. The identification of HIF-1alpha and AP-1 in ethanol-induced RANTES expression provides new strategies to ameliorate ethanol-induced inflammatory responses.
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