The Impact of Acute or Chronic Alcohol Intake on the NF-κB Signaling Pathway in Alcohol-Related Liver Disease

• Published in: International journal of molecular sciences 2020-12, Vol.21 (24), p.9407
• Main Authors: Nowak, Aleksander J, Relja, Borna
• Format: Article
• Language: English
• Subjects: Alcohol Drinking - adverse effects; Alcohol Drinking - metabolism; Alcohol use; Alcohol withdrawal; Alcoholism; Animals; Deoxyribonucleic acid; DNA; Drug withdrawal; Ethanol; Ethanol - pharmacokinetics; Ethanol - toxicity; Fatty acids; Gene expression; Genetic modification; Hepatitis; Humans; Immunology; In vivo methods and tests; Inflammation; Innate immunity; Intoxication; Liver; Liver - drug effects; Liver - metabolism; Liver diseases; Liver Diseases, Alcoholic - metabolism; Lymphocytes B; Metabolism; Metabolites; Molecular modelling; Mortality; NF-kappa B - metabolism; NF-κB protein; Pathogenesis; Review; Signal Transduction; Transcription
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21249407

Ethanol misuse is frequently associated with a multitude of profound medical conditions, contributing to health-, individual- and social-related damage. A particularly dangerous threat from this classification is coined as alcoholic liver disease (ALD), a liver condition caused by prolonged alcohol overconsumption, involving several pathological stages induced by alcohol metabolic byproducts and sustained cellular intoxication. Molecular, pathological mechanisms of ALD principally root in the innate immunity system and are especially associated with enhanced functionality of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. NF-κB is an interesting and convoluted DNA transcription regulator, promoting both anti-inflammatory and pro-inflammatory gene expression. Thus, the abundancy of studies in recent years underlines the importance of NF-κB in inflammatory responses and the mechanistic stimulation of inner molecular motifs within the factor components. Hereby, in the following review, we would like to put emphasis on the correlation between the NF-κB inflammation signaling pathway and ALD progression. We will provide the reader with the current knowledge regarding the chronic and acute alcohol consumption patterns, the molecular mechanisms of ALD development, the involvement of the NF-κB pathway and its enzymatic regulators. Therefore, we review various experimental in vitro and in vivo studies regarding the research on ALD, including the recent active compound treatments and the genetic modification approach. Furthermore, our investigation covers a few human studies.