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The neuropeptide PACAP upregulates expression and release of cytokines and cell adhesion molecules in human microvascular endothelial cells via VPAC type 1 receptor
Author(s) -
Steinhoff A.,
Grevelhörster A.,
Schmidt W. E.,
Luger T. A.,
Steinhoff M.
Publication year - 2004
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.0906-6705.2004.0212bw.x
Subject(s) - downregulation and upregulation , vasoactive intestinal peptide , receptor , cell adhesion molecule , autocrine signalling , endothelial stem cell , microbiology and biotechnology , inflammation , endocrinology , icam 1 , pituitary adenylate cyclase activating peptide , biology , medicine , neuropeptide , chemistry , immunology , biochemistry , in vitro , gene
Pituitary adenylate cyclase‐activating peptide (PACAP) and vasoactive intestinal peptide (VIP) belong to the same superfamily of neuropeptides which exert their effects by activating G‐protein‐coupled receptors defined as PACAP. So far, three receptor subtypes exist (PAC1R, VPACR‐1 and VPACR‐2). Because, PACAP appears to play a crucial role in cutaneous inflammation and vasoregulation, we examined the expression and biological effects of this peptide in primary human dermal microvascular endothelial cells (HDMECs). We detected the expression of PACAP and VPAC type 1 receptor at RNA and protein level by RT‐PCR and immunohistochemistry, indicating an autocrine regulatory mechanism. cAMP assays revealed VPAC1R to be functional in these cells. RT‐PCR showed upregulation of IL‐8 in a time‐ and dose‐dependent manner. ELISA experiments confirmed release of IL‐8 by HDMEC cells. We also investigated cell adhesion molecule expression after stimulation with PACAP. ICAM‐1 mRNA was upregulated at 3 and 6 h after treatment with PACAP, while VCAM was only upregulated maximally at 6 h after PACAP stimulation, indicating the regulation of cell adhesion molecule expression in human dermal endothelial cells via VPAC1R. Immunoreactivity for VPAC‐1R was enhanced in microvascular endothelial cells of patients with atopic dermatitis and urticaria, indicating upregulation of this receptor in endothelial cells during cutaneous inflammation. In summary, VIP and PACAP may play an important role in cutaneous neurogenic inflammation by activating VPAC‐1R on dermal microvascular endothelial cells.