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

This Article Full Text Full Text (PDF) All Versions of this Article: M500337-JLR200v1 46/11/2497    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Giltiay, N. V. Articles by Nikolova-Karakashian, M. N. Search for Related Content PubMed PubMed Citation Articles by Giltiay, N. V. Articles by Nikolova-Karakashian, M. N. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 46, 2497-2505, November 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Ceramide- and ERK-dependent pathway for the activation of CCAAT/enhancer binding protein by interleukin-1ß in hepatocytes

Natalia V. Giltiay¹, Alexander A. Karakashian¹, Alexander P. Alimov¹, Sandy Ligthle and Mariana N. Nikolova-Karakashian²

Department of Physiology, University of Kentucky College of Medicine, Lexington, KY 40536

Published, JLR Papers in Press, August 16, 2005. DOI 10.1194/jlr.M500337-JLR200

¹ N. V. Giltiay, A. A. Karakashian, and A. P. Alimov contributed equally to this work.

² To whom correspondence should be addressed. e-mail: mnikolo{at}uky.edu

Interleukin-1ß (IL-1ß) is a major inducer of liver acute-phase protein expression in response to infection. Several transcription factors, including CCAAT/enhancer binding protein (C/EBP), are known mediators in this process, although the mechanisms by which they modulate IL-1ß's action are not completely understood. Activation of sphingomyelinase (SMase) and the subsequent generation of ceramide are early steps in the IL-1ß signaling cascade. In this study, we investigate the role of ceramide in the IL-1ß regulation of C/EBP in primary hepatocytes. The C/EBP DNA binding activity was found to increase in a dose-dependent manner after stimulation with IL-1ß and exogenous addition of C₂-ceramide or treatment with SMase. These changes were accompanied by an increase in the nuclear content of C/EBPß. Both IL-1ß and ceramide led to extracellular signal-regulated kinase 1/2 (ERK1/2) activation as early as 15 min after treatment. Furthermore, the increase of cellular ceramide content resulted in increased phosphorylation of C/EBPß at serine 105 at later time points. Concurrently, the cytosolic levels of C/EBPß decreased, suggesting that IL-1ß and ceramide induced nuclear translocation of C/EBPß. Ceramide-induced C/EBPß phosphorylation, translocation, and DNA binding were suppressed by the addition of PD98059, an inhibitor of ERK1/2 phosphorylation.

These results suggest that ceramide and ERK mediate a pathway in the IL-1ß signaling cascade, which results in rapid posttranslational activation of C/EBPß.

Abbreviations: AGP, ₁-acid glycoprotein; AP-1, Activator Protein-1; APP, acute-phase protein; APR, acute-phase response; APRE, acute-phase response element; C/EBP, CCAAT/enhancer binding protein; ERK, extracellular signal-regulated kinase; IL-1ß, interleukin-1ß; JNK, c-Jun NH₂-terminal kinase; LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinase; MEK, mitogen-activated protein kinase kinase; NFB, nuclear factor B; nSMase, neutral sphingomyelinase; SerX, serine X; SM, sphingomyelin; SMase, sphingomyelinase

Supplementary key words inflammation • sphingomyelinase • liver • acute-phase protein • extracellular signal-regulated kinase

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				I. Komuro, T. Sunazuka, K. S. Akagawa, Y. Yokota, A. Iwamoto, and S. Omura Erythromycin derivatives inhibit HIV-1 replication in macrophages through modulation of MAPK activity to induce small isoforms of C/EBP{beta} PNAS, August 26, 2008; 105(34): 12509 - 12514. [Abstract] [Full Text] [PDF]

				A. Saha, C. E. Hammond, M. Gooz, and A. J. Smolka IL-1beta modulation of H,K-ATPase {alpha}-subunit gene transcription in Helicobacter pylori infection Am J Physiol Gastrointest Liver Physiol, April 1, 2007; 292(4): G1055 - G1061. [Abstract] [Full Text] [PDF]

				F. Gaccioliy, C. C. Huang, C. Wang, E. Bevilacqua, R. Franchi-Gazzola, G. C. Gazzola, O. Bussolati, M. D. Snider, and M. Hatzoglou Amino Acid Starvation Induces the SNAT2 Neutral Amino Acid Transporter by a Mechanism That Involves Eukaryotic Initiation Factor 2{alpha} Phosphorylation and cap-independent Translation J. Biol. Chem., June 30, 2006; 281(26): 17929 - 17940. [Abstract] [Full Text] [PDF]