Fibrinogen regulates the expression of inflammatory chemokines through NF-κB activation of endothelial cells

Min Guo, Sanjeev Sahni, Abha Sahni, Charles W. Francis

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The objective of this study was to characterize the role of fibrinogen in stimulating expression of inflammatory chemokines in endothelial cells through NF-κB activation. Human umbilical vein endothelial cells (HUVEC) were exposed to fibrinogen up to 3,000 μg/ml, and NF-κB activation was assessed using electrophoretic mobility shift assay (EMSA). Fibrinogen exposure resulted in a concentration dependent increase in NF-κB activation that reached a maximum at 1,000 μg/ml after 4 hours and was sustained up to 24 hours. The effect was inhibited by antibodies to αvβ3 and α5β1 and by the GRGDS peptide, indicating integrin involvement. Preincubation with Mn2+ lowered the fibrinogen concentration-dependence, consistent with integrin activation. Supershift assays demonstrated involvement of the p50, p65 and c-Rel components of NF-κB. Fibrinogen exposure also resulted in up-regulation of expression of monocyte chemoattractant protein-I (MCP-I and of interleukin-8 as shown by RNase protection assays and by real-time RT-PCR. Increased secretion of MCP-I was confirmed by ELISA. Parthenolide, an IκB kinase inhibitor, prevented up-regulation of MCP-I by fibrinogen, linking this response to NF-κB activation. From our findings, we conclude that fibrinogen regulates NF-κB activation and expression of inflammatory chemokines in endothelial cells and may be involved in mediating inflammatory processes.

Original languageEnglish (US)
Pages (from-to)858-866
Number of pages9
JournalThrombosis and Haemostasis
Volume92
Issue number4
DOIs
StatePublished - Oct 2004
Externally publishedYes

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Chemokines
Fibrinogen
Endothelial Cells
Integrins
glycyl-arginyl-glycyl-aspartyl-serine
Monocyte Chemoattractant Proteins
Up-Regulation
Human Umbilical Vein Endothelial Cells
Electrophoretic Mobility Shift Assay
Ribonucleases
Interleukin-8
Real-Time Polymerase Chain Reaction
Phosphotransferases
Enzyme-Linked Immunosorbent Assay
Peptides
Antibodies

Keywords

  • Chemokines
  • Endothelial cells
  • Fibrinogen
  • NF-κB

ASJC Scopus subject areas

  • Hematology

Cite this

Fibrinogen regulates the expression of inflammatory chemokines through NF-κB activation of endothelial cells. / Guo, Min; Sahni, Sanjeev; Sahni, Abha; Francis, Charles W.

In: Thrombosis and Haemostasis, Vol. 92, No. 4, 10.2004, p. 858-866.

Research output: Contribution to journalArticle

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