Journal article
Prolonged Ethanol Treatment Enhances Lipopolysaccharide/Phorbol Myristate Acetate-Induced Tumor Necrosis Factor-α Production in Human Monocytic Cells
Alcoholism, clinical and experimental research, Vol.25(3), pp.444-449
Received for publication May 17, 2000; accepted December 11, 2000.
03/2001
DOI: 10.1111/j.1530-0277.2001.tb02233.x
PMID: 11290857
Abstract
Background: Ethanol (EtOH) is known to alter host immune responses and cytokine production. Acute EtOH exposure can suppress tumor necrosis factor (TNF)-α production, which attenuates pulmonary defense against infection. Previous studies in our laboratory show that acute EtOH inhibited TNF-α production by a posttranscriptional process, namely suppression of TNF-α-converting, enzyme-mediated, ectodomain shedding. However, chronic EtOH has been shown to augment TNF-α production, and this has been associated with EtOH-induced liver injury. To further characterize this paradoxical effect of EtOH on TNF-α production, we developed an in vitro model by using Mono Mac 6 cells, a human monocytic cell line.
Methods: Mono Mac 6 cells were treated with EtOH (0–75 mM) for 1 to 7 days. TNF-α production was induced by lipopolysaccharide and phorbol myristate acetate and quantitated by enzyme-linked immunosorbent assay. Generation of reactive oxygen species (ROS) was assayed by using a specific fluorogenic reagent.
Results: Acute EtOH initially inhibited lipopolysaccharide/phorbol myristate acetate-induced TNF-α production in Mono Mac 6 cells. However, during chronic EtOH exposure, this inhibition was reversed gradually over time. By day 6 after EtOH treatment, Mono Mac 6 cells demonstrated significant up-regulation of TNF-α production. Moreover, chronic EtOH induced the generation of ROS in these Mono Mac 6 cells. Scavenging ROS by Mn(III)tetrakis(1-methyl-4pyridyl)porphyrin pentachloride and N-acetyl-L-cysteine attenuated chronic EtOH-enhanced TNF-α production.
Conclusion: These results suggest that ROS induction is involved in EtOH-enhanced TNF-α production by monocytes. This study also provides insight into the mechanisms of alteration of TNF-α production in different EtOH exposure settings.
Details
- Title: Subtitle
- Prolonged Ethanol Treatment Enhances Lipopolysaccharide/Phorbol Myristate Acetate-Induced Tumor Necrosis Factor-α Production in Human Monocytic Cells
- Creators
- Zili Zhang - Louisiana State UniversityGregory J. Bagby - Louisiana State UniversityDavid Stoltz - Louisiana State UniversityPeter Oliver - Louisiana State UniversityPaul O. Schwarzenberger - Louisiana State UniversityJay K. Kolls - Louisiana State University
- Resource Type
- Journal article
- Publication Details
- Alcoholism, clinical and experimental research, Vol.25(3), pp.444-449
- Edition
- Received for publication May 17, 2000; accepted December 11, 2000.
- DOI
- 10.1111/j.1530-0277.2001.tb02233.x
- PMID
- 11290857
- NLM abbreviation
- Alcohol Clin Exp Res
- ISSN
- 0145-6008
- eISSN
- 1530-0277
- Publisher
- Blackwell Publishing Ltd
- Number of pages
- 6
- Language
- English
- Date published
- 03/2001
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984297602302771
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