Adrenomedullin reduces expression of adhesion molecules on lymphatic endothelial cells.
Adrenomedullin (AM) is a novel vasoactive peptide which regulates vascular tone and vascular endothelial cell growth. We recently reported that lymphatic endothelial cells (LECs) are also an attractive target of AM and concluded that AM is a potent mediator of lympangiogenesis. In the present study, we conducted a genome-wide analysis of genes that are regulated by AM in LECs. AM profoundly suppressed gene expression of cell adhesion receptors and inflammatory factors in LECs, such as intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), endothelial adhesion molecule-1 (E-selectin), interleukin-8, and chemokines, QRT-PCR and flow cytometry analysis showed that AM dose-dependently suppressed the TNF-a-induced mRNA and protein expression of ICAM-1 and VCAM-l. Treatment of LECs with a cell permeable cyclic adenosine monophosphate (cAMP) analog, 8-Br-cAMP, mimicked the suppressive effect of AM on the expression of adhesion molecules. Moreover, both AM and 8-Br-cAMP suppressed TNF-α-induced NF-κB activation in LECs, indicating that AM reduces expression of adhesion molecules in LECs via a cAMP/NF-kB dependent pathway. These results suggest that AM may have an important role in the regulation of the expression of adhesion molecules in lymphatic endothelium, which is critical in the control of immune and inflammatory responses.
Jin
Donghao
D
Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, Osaka, Japan.
Otani
Kentaro
K
Yamahara
Kenichi
K
Ikeda
Tomoaki
T
Nagaya
Noritoshi
N
Kangawa
Kenji
K
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D053607:Adrenomedullin / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D015536:Down-Regulation; D019040:E-Selectin / Q000096:biosynthesis; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D055106:Genome-Wide Association Study; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D016328:NF-kappa B / Q000378:metabolism; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016328:NF-kappa B; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D053607:Adrenomedullin; D015124:8-Bromo Cyclic Adenosine Monophosphate