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Critical Reviews™ in Immunology
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ISSN Imprimer: 1040-8401
ISSN En ligne: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v32.i4.20
pages 307-320

Neuronal Derivative Mediators That Regulate Cutaneous Inflammations

Norihisa Mikami
Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, JAPAN
So-ichiro Fukada
Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, JAPAN
Hiroshi Yamamoto
Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, JAPAN
Kazutake Tsujikawa
Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, JAPAN


Allergic diseases accompanied by skin inflammation are intricately regulated by several mediators. Among these molecules, neurotransmitters are known to affect several immune cells such as T cells, B cells, dendritic cells, and mast cells. Neurotransmitters are released from nerve endings, and most of them work through specific G-protein coupled receptors. In this review, we discuss the interactions of representative neurotransmitters, calcitonin gene-related peptide (CGRP), substance P (SP), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase-activating polypeptide (PACAP), and prostaglandins (PGs), as well as their receptor signaling systems such as the cAMP/protein kinase A (PKA) pathway, phospholipase C (PLC) activation, and calcium ion channel activation, in cutaneous immunity.
Although many studies have proposed that these neurotransmitters play several roles in mouse contact hypersensitivity (CHS) models, human allergic contact dermatitis (ACD), and atopic dermatitis (AD), their physiological effects are controversial due to the diverse and complex mechanisms of skin inflammation. Both Th1- and Th2-mediated skin inflammation are well known, and neurotransmitters affect the kinds of inflammatory cells and subsequent immune reactions in them. In addition, the characteristics of antigen-presenting cells are also different in Th1- or Th2-mediated immune responses. Therefore, we take particular note of the type of skin inflammation, Th1- or Th2-mediated, and review the physiological roles of the neurotransmitters in skin inflammation.

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