Premium
Prolonged Ethanol Treatment Enhances Lipopolysaccharide/Phorbol Myristate Acetate‐Induced Tumor Necrosis Factor‐α Production in Human Monocytic Cells
Author(s) -
Zhang Zili,
Bagby Gregory J.,
Stoltz David,
Oliver Peter,
Schwarzenberger Paul O.,
Kolls Jay K.
Publication year - 2001
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2001.tb02233.x
Subject(s) - tumor necrosis factor alpha , lipopolysaccharide , phorbol , chemistry , cytokine , reactive oxygen species , tetradecanoylphorbol acetate , cell culture , biochemistry , microbiology and biotechnology , pharmacology , biology , immunology , protein kinase c , signal transduction , genetics
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.