PMID- 15467918
OWN - NLM
STAT- MEDLINE
DCOM- 20050518
LR  - 20220317
IS  - 0340-6245 (Print)
IS  - 0340-6245 (Linking)
VI  - 92
IP  - 4
DP  - 2004 Oct
TI  - Fibrinogen regulates the expression of inflammatory chemokines through NF-kappaB 
      activation of endothelial cells.
PG  - 858-66
AB  - The objective of this study was to characterize the role of fibrinogen in 
      stimulating expression of inflammatory chemokines in endothelial cells through 
      NF-kappaB activation. Human umbilical vein endothelial cells (HUVEC) were exposed 
      to fibrinogen up to 3,000 microg/ml, and NF-kappaB activation was assessed using 
      electrophoretic mobility shift assay (EMSA). Fibrinogen exposure resulted in a 
      concentration dependent increase in NF-kappaB activation that reached a maximum 
      at 1,000 microg/ml after 4 hours and was sustained up to 24 hours. The effect was 
      inhibited by antibodies to alpha(v)beta(3) and alpha(5)beta(1) and by the GRGDS 
      peptide, indicating integrin involvement. Preincubation with Mn(2+) lowered the 
      fibrinogen concentration-dependence, consistent with integrin activation. 
      Supershift assays demonstrated involvement of the p50, p65 and c-Rel components 
      of NF-kappaB. Fibrinogen exposure also resulted in up-regulation of expression of 
      monocyte chemoattractant protein-1 (MCP-1) and of interleukin-8 as shown by RNase 
      protection assays and by real-time RT-PCR. Increased secretion of MCP-1 was 
      confirmed by ELISA. Parthenolide, an IkappaB kinase inhibitor, prevented 
      up-regulation of MCP-1 by fibrinogen, linking this response to NF-kappaB 
      activation. From our findings, we conclude that fibrinogen regulates NF-kappaB 
      activation and expression of inflammatory chemokines in endothelial cells and may 
      be involved in mediating inflammatory processes.
FAU - Guo, Min
AU  - Guo M
AD  - Hematology-Oncology Unit, Department of Medicine, University of Rochester School 
      of Medicine and Dentistry, Rochester, NY 14642, USA.
FAU - Sahni, Sanjeev K
AU  - Sahni SK
FAU - Sahni, Abha
AU  - Sahni A
FAU - Francis, Charles W
AU  - Francis CW
LA  - eng
GR  - HL-30616/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokines)
RN  - 0 (Integrins)
RN  - 0 (Interleukin-8)
RN  - 0 (NF-kappa B)
RN  - 9001-32-5 (Fibrinogen)
SB  - IM
MH  - Chemokine CCL2/genetics/metabolism
MH  - Chemokines/*genetics
MH  - Dose-Response Relationship, Drug
MH  - Endothelium, Vascular/*cytology/metabolism
MH  - Fibrinogen/pharmacology/*physiology
MH  - Gene Expression Regulation/*physiology
MH  - Humans
MH  - Inflammation/genetics
MH  - Integrins/physiology
MH  - Interleukin-8/genetics
MH  - NF-kappa B/*physiology
MH  - Umbilical Veins/cytology
MH  - Up-Regulation
EDAT- 2004/10/07 09:00
MHDA- 2005/05/19 09:00
CRDT- 2004/10/07 09:00
PHST- 2004/10/07 09:00 [pubmed]
PHST- 2005/05/19 09:00 [medline]
PHST- 2004/10/07 09:00 [entrez]
AID - 04100858 [pii]
AID - 10.1160/TH04-04-0261 [doi]
PST - ppublish
SO  - Thromb Haemost. 2004 Oct;92(4):858-66. doi: 10.1160/TH04-04-0261.