Acute ethanol exposure inhibits macrophage IL-6 production: role of p38 and ERK1/2 MAPK.
Acute ethanol consumption has been linked to an increase in infectious complications in trauma and burn patients. Ethanol modifies production of a variety of macrophage-derived immunoregulatory mediators. Lipopolysaccharide (LPS), a potent stimulator of inflammatory responses in macrophages, activates several intracellular signaling pathways, including mitogen-activated protein kinases (MAPK). In the current study, we investigated the effect of acute ethanol exposure on in vivo activation of p38 and extracellularly regulated kinases 1 and 2 (ERK1/2) MAPK in murine macrophages and the corresponding, LPS-stimulated interleukin (IL)-6 production. We demonstrated that a single dose of ethanol transiently down-regulated p38 and ERK1/2 activation levels (3-24 h after treatment) and impaired IL-6 synthesis. Ethanol-related reduction in IL-6 production was not further affected by the presence of inhibitors of p38 and ERK1/2 (SB 202190 and PD 98059, respectively). These results demonstrate that acute ethanol exposure can impair macrophage IL-6 production and indicate that this effect may result from ethanol-induced alterations in intracellular signaling through p38 and ERK1/2.
Goral
Joanna
J
Department of Cell Biology, Loyola University Medical Center, Maywood, IL 60153, USA.
Choudhry
Mashkoor A
MA
Kovacs
Elizabeth J
EJ
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases
D000276:Adjuvants, Immunologic; D015850:Interleukin-6; D008070:Lipopolysaccharides; D000431:Ethanol; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases