1. ¹Department of Dermatology and Venereology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
2. ²Institute of Immunology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
3. ³IMTM, Magdeburg, Germany
4. ⁴Department of Pathobiochemistry, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
5. ⁵Institute of Experimental Internal Medicine, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
6. ⁶Department of Biochemistry and Biotechnology, Institute of Biochemistry, Martin-Luther-University Halle Wittenberg, Wittenberg, Germany
7. ⁷Departments of Dermatology and Immunology, Dessau Medical Center, Dessau, Germany
8. ⁸Laboratory for Biogerontology, Dermato-Pharmacology and Dermato-Endocrinology, Institute of Clinical Pharmacology and Toxicology, Charité Universitaetsmedizin Berlin, Berlin, Germany

Correspondence: Dr Anja Thielitz, Department of Dermatology and Venereology, Otto-von-Guericke University, Leipziger Str. 44, Magdeburg 39120, Germany. E-mail: anja.thielitz@medizin.uni-magdeburg.de

Received 2 September 2005; Revised 13 March 2006; Accepted 25 April 2006; Published online 15 June 2006.

Abstract

Acne is a chronic disease hallmarked by sebaceous hyperplasia, follicular hyperkeratosis, and inflammation. Parallel targeting of these factors is required to treat acne effectively. Inhibitors of dipeptidyl peptidase IV (DP IV) and aminopeptidase N (APN) show strong anti-inflammatory effects on immune cells and therapeutic efficacy in autoimmune disorders. Our investigation focused on the expression and functional relevance of these ectopeptidases in three cell types which exhibit an altered phenotype in early acne lesions. We showed for the first time expression of DP IV and APN on human sebocytes. In the SZ95 sebocyte cell line, the DP IV inhibitors Lys[Z(NO₂)]-thiazolidide and Lys[Z(NO₂)]-pyrrolidide and the APN inhibitors actinonin and bestatin suppressed proliferation, enhanced terminal differentiation, and slightly decreased total neutral lipid production. The anti-inflammatory and differentiation-restoring cytokine IL-1 receptor antagonist was significantly upregulated in SZ95 sebocytes and the HaCaT keratinocyte cell line in the presence of inhibitors. Furthermore, the inhibitors suppressed proliferation and IL-2 production of Propionibacterium acnes-stimulated T cells ex vivo and enhanced the expression of the immunosuppressive cytokine transforming growth factor-1. Our data provide first evidence for a functional role of DP IV and APN in the sebaceous gland apparatus and for their inhibitors, used alone or in combination, as completely new substances possibly affecting acne pathogenesis in a therapeutic manner.