Activation of cell-survival transcription factor NFκB in L1Ig6-stimulated endothelial cells

Martin Reidy, Pius Zihlmann, Jeffrey A. Hubbell, Heike Hall

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Ligation of the integrin αvβ3 in endothelial cells has been shown to be important for their survival. Such ligation induces signalling events merging into the Raf-Ras-ERK cascade that eventually induces activation of nuclear factor kappa B (NFκB), leading to its phosphorylation and nuclear translocation and thus inhibiting apoptosis. Here, the recombinant sixth immunoglobulin-like domain of cell adhesion molecules L1 (L1Ig6), a ligand for integrin αvβ 3, was explored as a component of vascular implant surfaces to initiate the NFκB-cell survival pathway. This supposition was supported. Specifically, NFκB-p65 was expressed in human umbilical vein endothelial cells (HUVECs) and when stimulated on L1Ig6, the phosphorylated form was found in the nucleus in over 60% of the cells. NFκB was not translocated into the nucleus on a number of other extracellular matrix substrates examined or when fibroblasts were cultured on L1Ig6. NFκB phosphorylation and nuclear translocation could be inhibited by blocking ligation of α vβ3 by L1Ig6 with an antibody recognizing αvβ3, with a cyclic RGD peptide, and with soluble L1Ig6. Moreover, blocking of αvβ3 interaction with L1Ig6 was correlated with induction of apoptosis. Thus, these experiments demonstrate that L1Ig6 may be useful as αvβ 3 ligand for the induction of endothelial survival pathways mediated by NFκB-p65.

Original languageEnglish (US)
Pages (from-to)542-550
Number of pages9
JournalJournal of Biomedical Materials Research - Part A
Volume77
Issue number3
DOIs
StatePublished - Jun 1 2006

Keywords

  • Apoptosis
  • Cell survival
  • Endothelial cells
  • HUVECs
  • NFκB

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials

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