Endothelial cell anergy is mediated by bFGF through the sustained activation of p38-MAPK and NF-κB inhibition

Vincenzo Flati, L. I. Pastore, A. W. Griffioen, S. Satijn, E. Toniato, I. D'Alimonte, E. Laglia, P. Marchetti, A. Gulino, S. Martinotti

Research output: Contribution to journalArticle

Abstract

Tumors escape from immune surveillance by, among other mechanisms, the down- regulation of endothelial adhesion molecules, such as ICAM-1, and by unresponsiveness to inflammatory signals, a process mediated by angiogenic factors that is called endothelial cell anergy. Here we present the cell biological regulation of these processes. The angiogenic basic fibroblast growth factor (bFGF/FGF-2) was found to inhibit tumor necrosis factor-α (TNF-α)- induced elevation of ICAM-1, at transcriptional level. Furthermore, we found that bFGF inhibits the TNF-mediated activation of NF-κB by blocking phosphorylation and degradation of IκBα. We also found that bFGF induces hyperphosphorylation of p38 MAPK on endothelial cells, whereas inhibition of such kinase abrogates the effect of bFGF on the TNF-mediated activation of NF-κB. Thus, we suggest that bFGF acts as an inhibitor of leukocyte adhesion in tumor vessels by decreasing the ICAM-1 expression through the sustained activation of p38-MAPK and via inhibition of NF-κB.

Original languageEnglish
Pages (from-to)761-773
Number of pages13
JournalInternational Journal of Immunopathology and Pharmacology
Volume19
Issue number4
Publication statusPublished - Oct 2006

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Keywords

  • Angiogenesis
  • bFGF
  • Endothelial cell anergy
  • ICAM-1
  • Mitogen-activated protein kinase
  • Nuclear factor-κB
  • TNF-α

ASJC Scopus subject areas

  • Pharmacology

Cite this

Flati, V., Pastore, L. I., Griffioen, A. W., Satijn, S., Toniato, E., D'Alimonte, I., Laglia, E., Marchetti, P., Gulino, A., & Martinotti, S. (2006). Endothelial cell anergy is mediated by bFGF through the sustained activation of p38-MAPK and NF-κB inhibition. International Journal of Immunopathology and Pharmacology, 19(4), 761-773.