ISSN:
1600-0625
Quelle:
Blackwell Publishing Journal Backfiles 1879-2005
Thema:
Medizin
Notizen:
AM and the sensory neuropeptide CGRP are potent vasoactive mediators that activate high-affinity G-protein-coupled receptors consisting of receptor-activity modifying proteins (RAMPs) and a seven-transmembrane domain calcitonin receptor-like receptor (CRLR) with RAMP-1/CRLR as CGRP and RAMP2 or -3/CRLR as AM receptors. In this study, we have examined the possibility that AM or CGRP modulate dermal microvascular EC adhesion molecule (ICAM-1 and VCAM-1) expression. Primary HDMEC or cells of the EC line HMEC-1 were transfected with cDNA expression vectors for an EGFP control, RAMP-1, RAMP-2 and CRLR by electroporation, or left untransfected. Stimulation of EC-overexpressing R1/CRLR or R2/CRLR with CGRP or AM (0.01–1000 nm) resulted in a dose-dependent upregulation of intracellular cAMP. Importantly, when HDMEC transfected with R1/CRLR or R2/CRLR were treated with TNFα in combination with CGRP or AM, these peptides interfered with the TNF-induced expression of ICAM-1 and VCAM-1 as well as the adhesion of lymphoblastoid cell lines to HDMEC monolayer in a biphasic manner. Likewise, AM and CGRP modulated the activation of nuclear factor κB (NF-κB) partly by inhibiting the TNFα-induced degradation of cytosolic IκBα. Neither transfection with the orphan CRLR nor RAMPs alone was capable of mediating a full reduction of TNFα-induced ICAM-1 or VCAM-1 expression. In conclusion, CGRP and more pronounced AM are capable of modulating TNFα-induced EC CAM expression, which may be of importance for the regulation of leucocyte–endothelial cell interaction during cutaneous neurogenic inflammation.This study was supported by the “Medizinische Forschungsgesellschaft Salzburg” and a grant of the Austrian Science Foundation (P14906).
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1111/j.0906-6705.2004.0212bu.x
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