Background: Fatty acid ethyl esters (FAEE), nonoxidative ethanol metabolites, are produced by the esterification of fatty acids and ethanol. Plasma and serum FAEE correlate linearly with blood ethanol levels and are present in organs most commonly damaged by ethanol abuse. Our previous studies have shown that there is significant synthesis of FAEE by human mononuclear cells within seconds of exposure to physiologic doses of ethanol.
Objectives: We studied the effects of FAEE on selected early events of mononuclear cell activation that follow stimulation with phytohemagglutinin (PHA). Fatty acid ethyl esters induced changes in cytosolic free calcium ([Ca2+]) levels, the production and secretion of interleukin-2 (IL-2) by the cells, and intracellular cAMP concentrations.
Methods: A mononuclear fraction of human white blood cells (WBC) was incubated with physiologic doses of FAEE. For experiments involving IL-2 production and calcium influx, PHA-stimulated cells were incubated with 10, 25, 50, or 100 microM ethyl oleate, a representative FAEE species, for 60 minutes. Interleukin-2 was measured by enzyme immunometeric assay and maximum levels of Ca2+ were monitored by spectrofluorimetry. In other experiments, mononuclear cells were incubated with 10, 25, and 50 microM ethyl oleate for 0.08 to 120 minutes, and then the concentration of cAMP was determined by a cAMP competitive enzyme immunoassay system.
Results: Fatty acid ethyl esters inhibited the PHA-induced IL-2 production and secretion in activated human mononuclear cells. Fatty acid ethyl esters also inhibited PHA-induced [Ca2+] influx into cells in a dose-dependent fashion. There was a rapid increase in the intracellular cAMP concentration of mononuclear cells induced by FAEE, with FAEE dose dependence. The cAMP concentration decreased as the incubation time with FAEE was increased.
Conclusions: Fatty acid ethyl esters inhibited PHA-stimulated IL-2 production and Ca2+ influx into human mononuclear cells and elevated intracellular cAMP concentration. These changes in mononuclear cell signaling may be associated with the immunosuppression associated with alcohol abuse.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/j.1530-0277.2006.00129.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Progressive systemic inflammation precedes decompensation in compensated cirrhosis.
JHEP Rep
February 2025
Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, Instituto Ramon y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, Madrid, Spain.
Background & Aims: Systemic inflammation is a driver of decompensation in cirrhosis with unclear relevance in the compensated stage. We evaluated inflammation and bacterial translocation markers in compensated cirrhosis and their dynamics in relation to the first decompensation.
Methods: This study is nested within the PREDESCI trial, which investigated non-selective beta-blockers for preventing decompensation in compensated cirrhosis and clinically significant portal hypertension (CSPH: hepatic venous pressure gradient ≥10 mmHg).
Antibiotic-mediated dysbiosis leads to activation of inflammatory pathways.
Front Immunol
January 2025
Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
Introduction: The gut microbiota plays a pivotal role in influencing host health, through the production of metabolites and other key signalling molecules. While the impact of specific metabolites or taxa on host cells is well-documented, the broader impact of a disrupted microbiota on immune homeostasis is less understood, which is particularly important in the context of the increasing overuse of antibiotics.
Methods: Female C57BL/6 mice were gavaged twice daily for four weeks with Vancomycin, Polymyxin B, or PBS (control).
Synergistic defecation effects of subsp. BL-99 and fructooligosaccharide by modulating gut microbiota.
Front Immunol
January 2025
Key Laboratory of Functional Dairy, Co-Constructed by Ministry of Education and Beijing Municipality, Department of Nutrition and Health, China Agricultural University, Beijing, China.
Introduction: Synbiotics have revealed the possibility of improving constipation through gut microbiota. The synergistic efficacy of subsp. lactis BL-99 (BL-99) and fructooligosaccharide (FOS) on constipation have not been investigated.
View Article and Find Full Text PDFIntegrated single-cell and bulk transcriptome analysis of R-loop score-based signature with regard to immune microenvironment, lipid metabolism and prognosis in HCC.
Front Immunol
January 2025
National Key Laboratory of Draggability Evaluation and Systematic Translational Medicine, Tianjin's Clinical Research Center for Cancer, Department of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
Background: Hepatocellular carcinoma (HCC) is one of the most prevalent causes of cancer-related morbidity and mortality worldwide. Late-stage detection and the complex molecular mechanisms driving tumor progression contribute significantly to its poor prognosis. Dysregulated R-loops, three-stranded nucleic acid structures associated with genome instability, play a key role in the malignant characteristics of various tumors.
View Article and Find Full Text PDFImpact of dysregulated microbiota-derived C18 polyunsaturated fatty acid metabolites on arthritis severity in mice with collagen-induced arthritis.
Front Immunol
January 2025
Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Kobe, Japan.
Objective: We aimed to evaluate microbiome and microbiota-derived C18 dietary polyunsaturated fatty acids (PUFAs), such as conjugated linoleic acid (CLA), and to investigate their differences that correlate with arthritis severity in collagen-induced arthritis (CIA) mice.
Methods: On day 84 after induction, during the chronic phase of arthritis, cecal samples were analyzed using 16S rRNA sequencing, and plasma and cecal digesta were evaluated using liquid chromatography-tandem mass spectrometry. Differences in microbial composition between 10 control (Ctrl) and 29 CIA mice or between the mild and severe subgroups based on arthritis scores were identified.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!