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. 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 pathophysiology of the disease. (J Allergy Clin Immunol 2003;111:1099-105.)