The Regulatory Mechanisms of Calcitonin Gene-related Peptide (CGRP) in Skin Inflammation

Abstract

Skin inflammation is one of several allergic symptoms that are regulated by several mediator molecules. One of these molecules, calcitonin gene-related peptide (CGRP) affects several immune cells including T cells, B cells, dendiritic cells and mast cells. CGRP binds to CGRP receptors composed of receptor activity-modifying protein 1 (RAMP1) and calcitonin receptor-like receptor (CLR) to modulate various functions such as pain transmission and vasodilation. Studies showing that CGRP physiologically regulates skin inflammation using a CGRP antagonist, capsaicin-induced depletion model, RAMP1-deficient mice and mouse contact hypersensitivity (CHS) model have been reported. Interestingly, while CGRP has inhibitory effects on Th1-mediated CHS, it was demonstrated that CGRP enhances Th2-mediated CHS response. Moreover, these skin inflammations were affected by elevated CGRP concentrations through an abnormal condition of the nervous system induced by exposure to psychological stress or neonatal chemical stimulation. In this review, we present the importance of CGRP in the regulation of skin inflammation under the several nervous conditions and provide a new insight into understanding various types of skin inflammation and skin diseases.