IMR Press / FBL / Volume 13 / Issue 6 / DOI: 10.2741/2850

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Article
The ectopeptidases dipeptidyl peptidase IV (DP IV) and aminopeptidase N (APN) and their related enzymes as possible targets in the treatment of skin diseases
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1 University Clinic of Dermatology and Venereology, Otto-von-Guericke University Magdeburg, Germany
2 IMTM GmbH, Department Immunopharm, Magdeburg, Germany
3 Institute of Immunology, Otto-von-Guericke University Magdeburg, Germany

*Author to whom correspondence should be addressed.

 

Front. Biosci. (Landmark Ed) 2008, 13(6), 2364–2375; https://doi.org/10.2741/2850
Published: 1 January 2008
(This article belongs to the Special Issue Dipeptidyl peptidase IV and related molecules in health and disease)
Abstract

Skin cells express dipeptidyl peptidase IV (DP IV) and aminopeptidase N (APN) and their related molecules of the DP IV-like family DP2, DP6, DP8, DP9 and fibroblast activation protein (FAP), as well as the cytoplasmic alanyl aminopeptidase (cAAP). The inhibitors of DP IV-like activity, Lys[Z(NO2)]-thiazolidide (LZNT) and Lys[Z(NO2)]-pyrrolidide (LZNP), and the APN inhibitors actinonin and bestatin affect proliferation, differentiation and cytokine production in sebocytes and keratinocytes, which are involved in the initiation of acne. Furthermore, they suppress proliferation of Propionibacterium acnes-stimulated T cells ex vivo and induce an anti-inflammatory cytokine profile. In the mouse tail model of psoriasis they have a pro-differentiative effect. In addition, these inhibitors suppress skin fibroblast proliferation, whereas only inhibition of DP IV-like activity decreases TGF-beta1 expression and abrogates the TGF-beta1 mediated stimulatory effects on TGF-beta1 and fibronectin production, collagen synthesis and matrix deposition in these cells. Targeting enzyme activity of DP IV and APN and their related molecules might be a novel approach for the treatment of acne, psoriasis or keloids.

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