title: Peptides with antimicrobial and anti-inflammatory activities that have therapeutic potential for treatment of acne vulgaris.
abstract: The pathogenesis of acne vulgaris is multifactorial involving infection of the pilosebaceous unit with Propionibacterium acnes and a cytokine-mediated inflammatory response. Five frog skin-derived antimicrobial peptides ([D4k]ascaphin-8, [G4K]XT-7, [T5k]temporin-DRa, brevinin-2GU, and B2RP-ERa), chosen for their low hemolytic activity against human erythrocytes, were assessed for their effects on the growth of clinical isolates of P. acnes and on the release of pro-inflammatory and anti-inflammatory cytokines from peripheral blood mononuclear (PBM) cells. All peptides inhibited the growth of P. acnes with the highest potency exhibited by [D4k]ascaphin-8 (minimum inhibitory concentration, MIC=3-12.5 μM). Release of TNF-α from concanavalin A (ConA)-stimulated PBM cells was significantly reduced by [D4k]ascaphin-8, [G4K]XT-7, brevinin-2GU, and B2RP-ERa (1 and 20 μg/ml) and by [T5k]temporin-DRa (20 μg/ml). Release of IFN-γ from unstimulated PBM cells was significantly reduced by [D4k]ascaphin-8 and brevinin-2GU (1 and 20 μg/ml). No peptide showed significant effects on Il-17 release. Release of the anti-inflammatory cytokines TGF-β, IL-4, and IL-10 from both unstimulated and ConA-treated PBM cells was significantly increased by [T5k]temporin-DRa and B2RP-ERa (1 and 20μg/ml). The potent activities of [D4k]ascaphin-8 and [T5k]temporin-DRa in inhibiting the growth of P. acnes and the release of pro-inflammatory cytokines, and in stimulating the release of anti-inflammatory cytokines suggest a possible therapeutic role in the treatment of acne vulgaris.
authors.affiliation: Department of Immunology and Microbiology, Faculty of Medicine, University of Kragujevac, Serbia.
authors.forename: Suzana
authors.initials: S
authors.lastname: Popovic
authors.forename: Edit
authors.initials: E
authors.lastname: Urbán
authors.forename: Miodrag
authors.initials: M
authors.lastname: Lukic
authors.forename: J Michael
authors.initials: JM
authors.lastname: Conlon
mesh_terms: D000152:Acne Vulgaris / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D000595:Amino Acid Sequence; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D001001:Anura; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D011425:Propionibacterium acnes / Q000187:drug effects* / Q000502:physiology; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000382:microbiology
chemical_list: D000893:Anti-Inflammatory Agents; D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; D003208:Concanavalin A