Prolonged ethanol treatment enhances lipopolysaccharide/phorbol myristate acetate-induced tumor necrosis factor-alpha production in human monocytic cells
Z. Zhang et al., Prolonged ethanol treatment enhances lipopolysaccharide/phorbol myristate acetate-induced tumor necrosis factor-alpha production in human monocytic cells, ALC CLIN EX, 25(3), 2001, pp. 444-449
Background: Ethanol (EtOH) is known to alter host immune responses and cyto
kine production. Acute EtOH exposure can suppress tumor necrosis factor (TN
F)-alpha production, which attenuates pulmonary defense against infection.
Previous studies in our laboratory show that acute EtOH inhibited TNF-alpha
production by a posttranscriptional process, namely suppression of TNF-alp
ha -converting, enzyme-mediated, ectodomain shedding. However. chronic EtOH
has been shown to augment TNF-alpha production, and this has been associat
ed with EtOH-induced liver injury. To further characterize this paradoxical
effect of EtOH on TNF-alpha 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-alpha production was induced by lipopolysaccharide and phorbol myrista
te acetate and quantitated by enzyme-linked immunosorbent assay. Generation
of reactive oxygen species (ROS) was assayed by using a specific flurogeni
c reagent.
Results: Acute EtOH initially inhibited lipopolysaccharide/phorbol myristat
e acetate-induced TNF-alpha production in Mono Mac 6 cells. However, during
chronic EtOH exposure, this inhibition was reversed gradually over time. B
y day 6 after EtOH treatment, Mono Mac 6 cells demonstrated significant upr
egulation of TNF-alpha production. Moreover, chronic EtOH induced the gener
ation of ROS in these Mono Mac 6 cells. Scavenging ROS by Mn(III)tetrakis(1
-methyl-4pyridyl)porphyrin pentachloride and N-aceryl-L-cysteine attenuated
chronic EtOH-enhanced TNF-alpha production.
Conclusion: These results suggest that ROS induction is involved in EtOH-en
hanced TNF-alpha production by monocytes. This study also provides insight
into the mechanisms of alteration of TNF-alpha production in different EtOH
exposure settings.