Stimulation of adhesion molecule expression in human endothelial cells (HUVEC) by adrenomedullin and corticotrophin.
Adrenomedullin (AM) and corticotrophin (ACTH) are both vasoactive peptides produced by a variety of cell types, including endothelial cells. Although AM and ACTH are considered to be important in the control of blood pressure and the response to stress, respectively, their role in inflammation and the immune response has not been clarified. This study shows, with the use of a cell-based ELISA, that AM and ACTH induce cell surface expression of the adhesion molecules E-selectin, VCAM-1, and ICAM-1 on human umbilical vein endothelial cells (HUVEC). Furthermore, this effect appears to be mediated in part via elevation of cAMP, given that both peptides elevate cAMP, the cell-permeable cAMP analog dibutyryl cAMP is able to mimic induction of all three cell adhesion molecules and the effect of AM and ACTH is inhibited by the adenylyl cyclase inhibitor SQ-22536. These findings demonstrate a role for AM and ACTH in the regulation of the immune and inflammatory response.
Hagi-Pavli
Eleni
E
Molecular Signalling Group, Clinical Science Research Centre, Barts & the London Queen Mary University of London, 2 Newark St., London E1 2AD, UK.
Farthing
Paula M
PM
Kapas
Supriya
S
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D053607:Adrenomedullin; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009994:Osmolar Concentration; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D000067956:Adenylyl Cyclase Inhibitors; D019040:E-Selectin; D016328:NF-kappa B; D010455:Peptides; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D053607:Adrenomedullin; C017759:9-(tetrahydro-2-furyl)-adenine; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D000225:Adenine