IL (interleukin)-6 exerts pro- as well as anti-inflammatory activities. Beside many other activities, IL-6 is the major inducer of acute phase proteins in the liver, acts as a differentiation factor for blood cells, as migration factor for T-cells and is a potent inducer of the chemokine MCP-1 (monocyte chemoattractant protein-1). Recent studies have focused on the negative regulation of IL-6 signal transduction through the IL-6-induced feedback inhibitors SOCS (suppressor of cytokine signalling) 1 and SOCS3 or the protein tyrosine phosphatases SHP-2 (Src homology 2 domain-containing protein tyrosine phosphatase 2) and TcPTP (T-cell protein tyrosine phosphatase). Studies on the cross-talk between pro-inflammatory mediators (IL-1, tumour necrosis factor, lipopolysaccharide) and IL-6 elucidated further regulatory mechanisms. Less is known about the regulation of IL-6 signal transduction by hormone/cytokine signalling through G-protein-coupled receptors. This is particularly surprising since many of these hormones (such as prostaglandins and chemokines) play an important role in inflammatory processes. In the present study, we have investigated the inhibitory activity of PGE1 (prostaglandin E1) on IL-6-induced MCP-1 expression and have elucidated the underlying molecular mechanism. Surprisingly, PGE1 does not affect IL-6-induced STAT (signal transducer and activator of transcription) 3 activation, but does affect ERK (extracellular-signal-regulated kinase) 1/2 activation which is crucial for IL-6-dependent expression of MCP-1. In summary, we have discovered a specific cross-talk between the adenylate cyclase cascade and the IL-6-induced MAPK (mitogen-activated protein kinase) cascade and have investigated its impact on IL-6-dependent gene expression.
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Research Article|
April 25 2008
Prostaglandin E1 inhibits IL-6-induced MCP-1 expression by interfering specifically in IL-6-dependent ERK1/2, but not STAT3, activation
Radoslaw M. Sobota;
Radoslaw M. Sobota
1Department of Biochemistry, Medical School, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany
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Pia J. Müller;
Pia J. Müller
1Department of Biochemistry, Medical School, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany
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Peter C. Heinrich;
Peter C. Heinrich
1Department of Biochemistry, Medical School, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany
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Fred Schaper
Fred Schaper
1
1Department of Biochemistry, Medical School, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany
1To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
November 19 2007
Revision Received:
February 13 2008
Accepted:
February 14 2008
Accepted Manuscript online:
February 14 2008
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem J (2008) 412 (1): 65–72.
Article history
Received:
November 19 2007
Revision Received:
February 13 2008
Accepted:
February 14 2008
Accepted Manuscript online:
February 14 2008
Citation
Radoslaw M. Sobota, Pia J. Müller, Peter C. Heinrich, Fred Schaper; Prostaglandin E1 inhibits IL-6-induced MCP-1 expression by interfering specifically in IL-6-dependent ERK1/2, but not STAT3, activation. Biochem J 15 May 2008; 412 (1): 65–72. doi: https://doi.org/10.1042/BJ20071572
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