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B Site in the Platelet Endothelial Cell Adhesion Molecule-1 Promoter1
*
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain; and
Departamento de Fisiología e Inmunología, Facultad de Medicina, Universidad de Córdoba, Córdoba, Spain
Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a type I
transmembrane adhesion protein of 130 kDa that belongs to a subgroup of
the Ig gene superfamily, characterized by the presence of
immunoreceptor tyrosine-based inhibitory motifs. PECAM-1 is
expressed in circulating platelets, monocytes, neutrophils, a selective
subgroup of T cells, and in endothelial cells, where it is
preferentially located at intercellular junctions and participates in
leukocyte transmigratory processes. The identification of two consensus
NF-
B sites within the PECAM-1 promoter led us to analyze their
possible involvement in the PECAM-1 expression regulated by
inflammatory stimuli. We found that surface expression and promoter
activity of PECAM-1 in myeloid cells are regulated by modulators of
NF-B, including TNF-
, PMA, and pyrrolidine dithiocarbamate.
Mobility shifts assays identified a specific NF-B-binding element at
+110/+120, whose mutation abolished the basal promoter activity of
PECAM-1 and decreased NF-B-dependent responses of the PECAM-1 gene
promoter. Furthermore, cotransfection experiments with an expression
vector encoding the p65 subunit of NF-B showed transactivation of
the PECAM-1 promoter. These results demonstrate that NF-B can
regulate the transcriptional activity of
PECAM-1.
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