Title: The role of purinergic signaling in development of irritant dermatitis of acrodermatitis enteropathica
Abstract: Purinergic signaling is crucial to maintain homeostasis of inflammation. We previously elucidated that disruption of the homeostasis of skin inflammation by Zn deficiency-mediated ablation of Langerhans cells (LCs) that expressed CD39 (ATP conversion protein) was causative for development of characteristic dermatitis in acrodermatitis enteropathica (AE). Basically, ATP was hydrolyzed into AMP by several molecules including CD39 and then AMP was converted into adenosine by CD73. We now investigated the role of a newly identified ATP conversion molecule, tissue non-specific alkaline phosphatase (TNAP), and AMP conversion molecule, CD73, in epidermis of Zn-adequate (ZA) and Zn-deficient (ZD) diet mice, since the role of these molecules in epidermis was still unknown. We confirmed only ATP, but not ADP and AMP, elicited skin inflammation after intradermal injection. Next, we found among murine alkaline phosphatase (ALP), TNAP was the sole ALP in epidermis, and was expressed both KCs and LCs with significant impaired expression in ZD mice compared with ZA mice, while CD73 was expressed KCs but not LCs, and the expression level was comparable between ZA and ZD mice. Next, we assessed if TNAP was involved in ATP degradation in epidermis. ATP release from Pam212 was measured after addition of 0.1% Benzalkonium chloride with or without TNAP inhibitor. ATP concentration was marginally impaired in the presence of TNAP inhibitor, suggesting that TNAP could degrade ATP, whereas another ATP conversion molecules existed in KCs. These data suggested that ablation of CD39- and TNAP-expressing LCs and impaired expression of TNAP in KCs resulted in development of irritant contact dermatitis of AE through accumulation of ATP after irritation, but AMP conversion by CD73 was intact in AE.
Publication Year: 2016
Publication Date: 2016-09-29
Language: en
Type: article
Indexed In: ['crossref']
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