Cyclic Adenosine Monophosphate Signaling in Inflammatory Skin DiseaseJack Levy1#, Dalee M Zhou1#and Jonathan H Zippin2*
- *Corresponding Author:
- Jonathan Zippin
Professor, Department of Dermatology
NYPH-Weill Cornell Medical Center
1305 York Avenue, 9th Floor
New York 10021, USA
E-mail: [email protected]
Received date: December 12, 2015 Accepted date: January 29, 2016 Published date: January 30, 2016
Citation: Levy J, Zhou DM, Zippin JH (2016) Cyclic Adenosine Monophosphate Signalling in Inflammatory Skin Disease. J Clin Exp Dermatol Res 7:326. doi: 10.4172/2155-9554.1000326
Copyright: © 2015 Patrice GI, et al. This is an open-access article distributed under the terms of the Creative Co mmons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The second messenger cyclic adenosine monophosphate (cAMP) regulates numerous key pathways that impact the immune system. Distinct cellular cAMP signaling pathways can lead to both pro- and anti-inflammatory effects depending upon the cell type. When dysregulated, these cAMP pathways can influence the pathogenesis of inflammatory cutaneous diseases, such as atopic dermatitis and psoriasis. In psoriasis and atopic dermatitis, cAMP and/or its effector proteins (e.g., protein kinase A) are downregulated suggesting that elevation of cAMP might be a therapeutic option. cAMP levels are the result of balance between synthesis by adenylyl cyclases and degradation by phosphodiesterases (PDEs). Pharmacologically inhibiting PDEs represents one effective mechanism to raise intracellular cAMP levels perhaps leading to targeted immune suppression. Several drugs have been developed to target PDEs and while some toxicities (e.g., nausea and emesis) exist these drugs are generally well tolerated. Perhaps the best characterized is Apremilast, a PDE4 specific inhibitor, which has been FDA approved for the treatment of psoriasis and shows great promise as a safe and novel immunosuppressive medication. Following on the heels of Apremilast are numerous oral and topical PDE inhibitors in various stages of clinical trials. In this review, we examine the role of cAMP signaling in inflammatory cutaneous diseases and the development of PDE inhibitors as therapeutics.