Down-regulation of vasoactive intestinal polypeptide receptor expression in atopic dermatitis.
BACKGROUND
Receptors for vasoactive intestinal polypeptide (VIP) have recently been suggested to play a key role in immunomodulation with genetically modified mice. However, it is not known whether changes in receptor gene regulation are involved in the pathogenesis of human immune disorders.


OBJECTIVE
We studied the expression of VPAC(2) in acute lesions of the human immune disease atopic dermatitis.


METHODS
By using nonradioactive in situ hybridization, quantitative immunohistochemistry, RT-PCR, and gene array studies, the expression status of VPAC(2) was assessed in atopic dermatitis and control tissues and in the human mast cell line HMC-1.


RESULTS
In situ hybridization and immunohistochemistry demonstrated VPAC(2) mRNA and protein expression in human mast cells surrounded by VIP positive nerve fibers. Gene array experiments and RT-PCR studies showed high levels of VPAC(2) mRNA expression in mast cells that were increased compared to other receptors such as VPAC(1) or VIP in the human mast cell line HMC-1. Stimulation of HMC-1 cells led to a downregulation of VPAC(2). Similarly, quantitative immunohistochemistry for VPAC(2) in acute atopic dermatitis lesions showed a significantly decreased VPAC(2) immunoreactivity in mast cells.


CONCLUSIONS
The downregulation of VPAC(2) in human mast cells in acute lesions of atopic dermatitis suggests a role of this G-protein;coupled receptor in the pathophysiology of the disease.
Clinical Research Unit of Allergology, Department of Pediatric Pneumology and Immunology, Charité School of Medicine, Humboldt-University, Berlin, Germany.
David A
DA
Groneberg
Pia
P
Welker
Tanja C
TC
Fischer
Q Thai
QT
Dinh
Andreas
A
Grützkau
Christian
C
Peiser
Ulrich
U
Wahn
Beate M
BM
Henz
Axel
A
Fischer
D003876:Dermatitis, Atopic / Q000378:metabolism*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D006801:Humans; D008407:Mast Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D018005:Receptors, Vasoactive Intestinal Peptide / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D012867:Skin / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D012333:RNA, Messenger; D018005:Receptors, Vasoactive Intestinal Peptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D014660:Vasoactive Intestinal Peptide