1. ^*Department of Pharmacology, School of Medicine, Aristotle University, Thessaloniki, Greece
2. ^†Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece
3. ^‡Department of Dermatology, Charité University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany
4. ^§Division of Skin Oncologic Surgery-Plastic Surgery, School of Medicine, Aristotle University, Thessaloniki, Greece
5. ^¶Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany

Correspondence: Christos C. Zouboulis, Department of Dermatology, Charité University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany. Email: zouboulis@medizin.fu-berlin.de

¹The first 4 authors have contributed equally to this manuscript.

²The last 2 authors share senior authorship.

Received 1 May 2004; Revised 17 March 2005; Accepted 21 March 2005.

Abstract

Acne vulgaris is a skin disorder of the sebaceous follicles, involving hyperkeratinization and perifollicular inflammation. Matrix metalloproteinases (MMP) have a predominant role in inflammatory matrix remodeling and hyperproliferative skin disorders. We investigated the expression of MMP and tissue inhibitors of MMP (TIMP) in facial sebum specimens from acne patients, before and after treatment with isotretinoin. Gelatin zymography and Western-blot analysis revealed that sebum contains proMMP-9, which was decreased following per os or topical treatment with isotretinoin and in parallel to the clinical improvement of acne. Sebum also contains MMP-1, MMP-13, TIMP-1, and TIMP-2, as assessed by ELISA and western blot, but only MMP-13 was decreased following treatment with isotretinoin. The origin of MMP and TIMP in sebum is attributed to keratinocytes and sebocytes, since we found that HaCaT keratinocytes in culture secrete proMMP-2, proMMP-9, MMP-1, MMP-13, TIMP-1, and TIMP-2. SZ95 sebocytes in culture secreted proMMP-2 and proMMP-9, which was also confirmed by microarray analysis. Isotretinoin inhibited the arachidonic acid-induced secretion and mRNA expression of proMMP-2 and -9 in both cell types and of MMP-13 in HaCaT keratinocytes. These data indicate that MMP and TIMP of epithelial origin may be involved in acne pathogenesis, and that isotretinoin-induced reduction in MMP-9 and -13 may contribute to the therapeutic effects of the agent in acne.