title: Isotretinoin therapy changes the expression of antimicrobial peptides in acne vulgaris.
abstract: In acne vulgaris, antimicrobial peptides (AMPs) could play a dual role; i.e., protective by acting against Propionibacterium acnes, pro-inflammatory by acting as signalling molecules. The cutaneous expression of 15 different AMPs was investigated in acne patients; furthermore, the impact of isotretinoin therapy on AMP expression was analysed in skin biopsies from 13 patients with acne vulgaris taken before, during and after a 6-month treatment cycle with isotretinoin using quantitative real-time polymerase chain reaction. Cutaneous expression of the AMPs cathelicidin, human β-defensin-2 (HBD-2), lactoferrin, lysozyme, psoriasin (S100A7), koebnerisin (S100A15), and RNase 7 was upregulated in untreated acne vulgaris, whereas α-defensin-1 (HNP-1) was downregulated compared to controls. While relative expression levels of cathelicidin, HBD-2, lactoferrin, psoriasin (S100A7), and koebnerisin (S100A15) decreased during isotretinoin treatment, only those of cathelicidin and koebnerisin returned to normal after 6 months of isotretinoin therapy. The increased expression of lysozyme and RNase 7 remained unaffected by isotretinoin treatment. The levels of granulysin, RANTES (CCL5), perforin, CXCL9, substance P, chromogranin B, and dermcidin were not regulated in untreated acne patients and isotretinoin had no effect on these AMPs. In conclusion, the expression of various AMPs is altered in acne vulgaris. Isotretinoin therapy normalizes the cutaneous production of distinct AMPs while the expression of others is still increased in healing acne. Considering the antimicrobial and pro-inflammatory role of AMPs, these molecules could serve as specific targets for acne therapy and maintenance of clinical remission.
authors.affiliation: Department of Dermatology and Allergology, Ludwig Maximilian University Munich, Frauenlobstr. 9-11, 80337, Munich, Germany.
authors.forename: Alena
authors.initials: A
authors.lastname: Borovaya
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Dombrowski
authors.forename: Stephanie
authors.initials: S
authors.lastname: Zwicker
authors.forename: Olga
authors.initials: O
authors.lastname: Olisova
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruzicka
authors.forename: Ronald
authors.initials: R
authors.lastname: Wolf
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schauber
authors.forename: Miklós
authors.initials: M
authors.lastname: Sárdy
mesh_terms: D000152:Acne Vulgaris / Q000188:drug therapy* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism*; D003879:Dermatologic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015474:Isotretinoin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D058990:Molecular Targeted Therapy; D011425:Propionibacterium acnes / Q000276:immunology*; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D055815:Young Adult; D023084:alpha-Defensins / Q000235:genetics / Q000378:metabolism; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D003879:Dermatologic Agents; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C510475:S100A7A protein, human; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; D015474:Isotretinoin; D054804:Cathelicidins