title: The ectopeptidases dipeptidyl peptidase IV (DP IV) and aminopeptidase N (APN) and their related enzymes as possible targets in the treatment of skin diseases.
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.
authors.affiliation: University Clinic of Dermatology and Venereology, Otto-von-Guericke University Magdeburg, Germany. anja.thielitz@med.ovgu.de
authors.forename: Anja
authors.initials: A
authors.lastname: Thielitz
authors.forename: Siegfried
authors.initials: S
authors.lastname: Ansorge
authors.forename: Ute
authors.initials: U
authors.lastname: Bank
authors.forename: Michael
authors.initials: M
authors.lastname: Tager
authors.forename: Sabine
authors.initials: S
authors.lastname: Wrenger
authors.forename: Harald
authors.initials: H
authors.lastname: Gollnick
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhold
mesh_terms: D000152:Acne Vulgaris / Q000188:drug therapy*; D000818:Animals; D018826:CD13 Antigens / Q000737:chemistry / Q000494:pharmacology*; D006224:Cricetinae; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005355:Fibrosis; D006801:Humans; D007249:Inflammation; D008647:Mesocricetus; D051379:Mice; D008954:Models, Biological; D011565:Psoriasis / Q000628:therapy; D012871:Skin Diseases / Q000378:metabolism*; D012878:Skin Neoplasms / Q000201:enzymology / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D018826:CD13 Antigens; D018819:Dipeptidyl Peptidase 4