ABSTRACT
Department of Dermatology and Boltzmann Institute for Cell-and Immunobiology of the Skin, University of Münster, 48129 Münster, Germany
The cutaneous nervous system regulates a variety of physiological and pathophysiological biological functions such as cellular development, growth, differentiation, immunity, inflammation, pruritus and tissue repair. Several structures and cells are involved including cutaneous nerve fibres, which release neuromediators and activate specific receptors on resident target cells or transient immune cells in the skin. Cutaneous neuromediators include different biochemical entities. Classical neurotransmitters such as catecholamines and acetylcholine are released from the autonomic nervous system or cutaneous cells to modulate inflammatory or immune functions in the epidermis and dermis via high-affinity receptors. Neuropeptides such as substance P, calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), or proopio-melano-corticotropins (POMC) peptides, for example, can be released from both sensory or autonomic nerve fibres to activate a variety of cutaneous cells through highaffinity neuropeptide receptors or by direct activation of intracellular G protein signalling cascades. Proteinases such as tryptase or neutral endopeptidase, for example, inactivate neuropeptides in the extracellular space or at the cell surface thereby terminating neuropeptide-induced inflammatory or immune responses. Proteinaseactivated receptors or vanilloid (capsaicin) receptors are recently described receptors which may have a high impact in regulating cutaneous neurogenic inflammation. Together, a close multidirectional interaction between neuromediators, high-affinity receptors and regulatory proteases on nerves, cutaneous cells and transient or permanent immunomodulatory cells are involved to maintain tissue integrity and regulate inflammatory responses in the skin.
