Fibronectin attachment activates the NF-kappa B p50/p65 heterodimer in fibroblasts and smooth muscle cells.
The nuclear factor kappa B, NF-kappa B, is activated by numerous inflammatory mediators, regulating biological responses that in part are dependent on the extracellular matrix. Analyses of the influence of cell-matrix interaction on NF-kappa B activation revealed that attachment to fibronectin caused an increase in NF-kappa B activity corresponding to 3-fold the level in cells plated on bare plastic. This effect was dependent on the degree of attachment and appeared to involve both the RGD motif of the cell-binding domain, and the heparin-binding domain of fibronectin. Fibronectin attachment specifically caused activation of the p50/p65 heterodimeric form of NF-kappa B, resulting in an increase of this complex to a level similar to that induced by cytokine stimulation. These data show that cell attachment has a pronounced influence on the level of NF-kappa B activity, affecting specific dimeric complexes, and suggest this to be a pathway through which effects depending on cell-matrix interaction can regulate cell behavior and cytokine responses.
Qwarnström
E E
EE
Department of Pathology, University of Washington, Seattle 98195.
Ostberg
C O
CO
Turk
G L
GL
Richardson
C A
CA
Bomsztyk
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005347:Fibroblasts / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D000882:Haplorhini; D006801:Humans; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D009838:Oligodeoxyribonucleotides; D051996:Transcription Factor RelA
D005353:Fibronectins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D009838:Oligodeoxyribonucleotides; D051996:Transcription Factor RelA