HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print November 21, 2003

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.0703350v1 75/3/553    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Goral, J. Articles by Kovacs, E. J. Search for Related Content PubMed PubMed Citation Articles by Goral, J. Articles by Kovacs, E. J.

© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0703350

Received for publication July 25, 2003.
Revised October 1, 2003.
Accepted for publication October 28, 2003.

Article

Acute ethanol exposure inhibits macrophage IL-6 production: role of p38 and ERK1/2 MAPK

Joanna Goral ^*, Mashkoor A. Choudhry ^@, and Elizabeth J. Kovacs ^*

Departments of *Cell Biology, Neurobiology and Anatomy and Surgery, Burn and Shock Trauma Institute, and Alcohol Research Program, Loyola University Medical Center, Maywood, Illinois

^@ To whom correspondence should be addressed. E-mail: ekovacs{at}lumc.edu.

	Abstract

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.

Key Words: lipopolysaccharide • inflammation • signal transduction • suppression

This article has been cited by other articles:

				G. Szabo, A. Dolganiuc, Q. Dai, and S. B. Pruett TLR4, Ethanol, and Lipid Rafts: A New Mechanism of Ethanol Action with Implications for other Receptor-Mediated Effects J. Immunol., February 1, 2007; 178(3): 1243 - 1249. [Abstract] [Full Text] [PDF]

				A. H. Lau, M. Abe, and A. W. Thomson Ethanol affects the generation, cosignaling molecule expression, and function of plasmacytoid and myeloid dendritic cell subsets in vitro and in vivo J. Leukoc. Biol., May 1, 2006; 79(5): 941 - 953. [Abstract] [Full Text] [PDF]

				S. B. Pruett, Q. Zheng, C. Schwab, and R. Fan Sodium Methyldithiocarbamate Inhibits MAP Kinase Activation through Toll-like Receptor 4, Alters Cytokine Production by Mouse Peritoneal Macrophages, and Suppresses Innate Immunity Toxicol. Sci., September 1, 2005; 87(1): 75 - 85. [Abstract] [Full Text] [PDF]

				J. Goral and E. J. Kovacs In Vivo Ethanol Exposure Down-Regulates TLR2-, TLR4-, and TLR9-Mediated Macrophage Inflammatory Response by Limiting p38 and ERK1/2 Activation J. Immunol., January 1, 2005; 174(1): 456 - 463. [Abstract] [Full Text] [PDF]