Downregulation 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 inummohistochemistry, 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 inummohistochemistry demonstrated VPAC2 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 VPAC2, 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 inummohistochemistry for VPAC(2) in acute atopic dermatitis lesions showed a significantly decreased VPAC(2) immunoreactivity in mast cells. Conclusion: 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 pathophysioIogy of the disease.