PMID- 18271757
OWN - NLM
STAT- MEDLINE
DCOM- 20080521
LR  - 20220408
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 412
IP  - 1
DP  - 2008 May 15
TI  - Prostaglandin E1 inhibits IL-6-induced MCP-1 expression by interfering 
      specifically in IL-6-dependent ERK1/2, but not STAT3, activation.
PG  - 65-72
LID - 10.1042/BJ20071572 [doi]
AB  - 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 PGE(1) 
      (prostaglandin E(1)) on IL-6-induced MCP-1 expression and have elucidated the 
      underlying molecular mechanism. Surprisingly, PGE(1) 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.
FAU - Sobota, Radoslaw M
AU  - Sobota RM
AD  - Department of Biochemistry, Medical School, RWTH Aachen University, 
      Pauwelsstrasse 30, 52074 Aachen, Germany.
FAU - Muller, Pia J
AU  - Muller PJ
FAU - Heinrich, Peter C
AU  - Heinrich PC
FAU - Schaper, Fred
AU  - Schaper F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Guanine Nucleotide Exchange Factors)
RN  - 0 (Interleukin-6)
RN  - 0 (RAPGEF3 protein, human)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 1F7A44V6OU (Colforsin)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.4.2.31 (Pertussis Toxin)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - F5TD010360 (Alprostadil)
SB  - IM
MH  - Alprostadil/*pharmacology
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/*genetics/metabolism
MH  - Colforsin/pharmacology
MH  - Cyclic AMP/pharmacology
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism/physiology
MH  - Down-Regulation/drug effects
MH  - Enzyme Activation/drug effects
MH  - Guanine Nucleotide Exchange Factors/metabolism
MH  - Humans
MH  - Interleukin-6/*pharmacology
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 1/*antagonists & inhibitors/metabolism
MH  - Mitogen-Activated Protein Kinase 3/*antagonists & inhibitors/metabolism
MH  - Pertussis Toxin/pharmacology
MH  - STAT3 Transcription Factor/*metabolism
MH  - Signal Transduction/drug effects
MH  - Substrate Specificity/drug effects
MH  - src-Family Kinases/physiology
EDAT- 2008/02/15 09:00
MHDA- 2008/05/22 09:00
CRDT- 2008/02/15 09:00
PHST- 2008/02/15 09:00 [pubmed]
PHST- 2008/05/22 09:00 [medline]
PHST- 2008/02/15 09:00 [entrez]
AID - BJ20071572 [pii]
AID - 10.1042/BJ20071572 [doi]
PST - ppublish
SO  - Biochem J. 2008 May 15;412(1):65-72. doi: 10.1042/BJ20071572.