PMID- 16427785
OWN - NLM
STAT- MEDLINE
DCOM- 20060801
LR  - 20161124
IS  - 1043-4666 (Print)
IS  - 1043-4666 (Linking)
VI  - 33
IP  - 1
DP  - 2006 Jan 7
TI  - Cardiotrophin-1 induces monocyte chemoattractant protein-1 synthesis in human 
      umbilical vein endothelial cells.
PG  - 46-51
AB  - In chronic heart failure (CHF) cardiotrophin-1 (CT-1) and monocyte 
      chemoattractant protein-1 (MCP-1) plasma concentrations are elevated. CT-1 is a 
      cytokine of the interleukin-6 (IL-6) superfamily. Most members of the IL-6 family 
      are able to activate human umbilical vein endothelial cells (HUVEC) but so far 
      there are no data which demonstrate that CT-1 can activate HUVEC. Because 
      MCP-1-as a marker of endothelial activation-is elevated in CHF we examined 
      whether CT-1 will induce MCP-1 production in HUVEC. MCP-1 mRNA levels were 
      determined by real time PCR, RT-PCR and northern blot analysis and MCP-1 protein 
      concentrations in the supernatant by ELISA. Signal transducer and activator of 
      transcription 3 (STAT3) and phosphorylated STAT3 (pSTAT3) were investigated by 
      western blot analysis. Incubation of HUVEC with different CT-1 concentrations for 
      various time periods induced time and concentration dependent MCP-1 mRNA. Maximal 
      MCP-1 mRNA was reached after 6h. After 24h CT-1 caused a significant induction of 
      MCP-1 protein in the supernatant compared to control. CT-1 induced concentration 
      dependent phosphorylation of STAT3 without any change in total-STAT3 
      concentration. Piceatannol-a specific blocker of STAT3 phosphorylation-inhibited 
      CT-1 induced MCP-1 induction completely. AG490-a blocker of the JAK2 pathway-was 
      also able to inhibit CT-1 induced MCP-1 upregulation, indicating that the JAK2 
      pathway is also necessary for MCP-1 induction. Parthenolide-a blocker of 
      NFkappaB-inhibited CT-1 induced MCP-1 expression, completely. Our data show that 
      CT-1 induces in a concentration and time dependent manner MCP-1 mRNA and protein 
      in HUVEC. STAT3 phosphorylation, the activation of JAK2 and NF-kappaB are 
      involved in this pathway. In CHF, CT-1 may be able to induce MCP-1 which might be 
      responsible for progression of heart failure either by recruiting inflammatory 
      cells within the myocardium or by a direct modulation of myocyte function.
FAU - Fritzenwanger, Michael
AU  - Fritzenwanger M
AD  - Department of Internal Medicine I, Division of Cardiology, 
      Friedrich-Schiller-University Jena, Erlanger Allee 101, 07740 Jena, Germany. 
      michael.fritzenwanger@med.uni-jena.de
FAU - Kuethe, Friedhelm
AU  - Kuethe F
FAU - Haase, Daniela
AU  - Haase D
FAU - Jandt, Enrico
AU  - Jandt E
FAU - Figulla, Hans-R
AU  - Figulla HR
LA  - eng
PT  - Journal Article
DEP - 20060119
PL  - England
TA  - Cytokine
JT  - Cytokine
JID - 9005353
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (RNA, Messenger)
RN  - 0 (STAT3 Transcription Factor)
RN  - AJ7U77BR8I (cardiotrophin 1)
SB  - IM
MH  - Cell Line
MH  - Chemokine CCL2/*metabolism
MH  - Cytokines/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Endothelium, Vascular/*metabolism
MH  - Humans
MH  - Phosphorylation
MH  - RNA, Messenger/metabolism
MH  - STAT3 Transcription Factor/metabolism/physiology
MH  - Time Factors
MH  - Umbilical Veins/*metabolism
EDAT- 2006/01/24 09:00
MHDA- 2006/08/02 09:00
CRDT- 2006/01/24 09:00
PHST- 2004/10/14 00:00 [received]
PHST- 2005/07/25 00:00 [revised]
PHST- 2005/11/23 00:00 [accepted]
PHST- 2006/01/24 09:00 [pubmed]
PHST- 2006/08/02 09:00 [medline]
PHST- 2006/01/24 09:00 [entrez]
AID - S1043-4666(05)00345-5 [pii]
AID - 10.1016/j.cyto.2005.11.016 [doi]
PST - ppublish
SO  - Cytokine. 2006 Jan 7;33(1):46-51. doi: 10.1016/j.cyto.2005.11.016. Epub 2006 Jan 
      19.