title: Skin sensitization to p-phenylenediamine: the diverging roles of oxidation and N-acetylation for dendritic cell activation and the immune response.
abstract: Skin is a target of allergic reactions to aromatic amine hair dye precursors, such as p-phenylenediamine (PPD). As conversion of PPD on or in the skin is expected to be required for the induction of allergic contact dermatitis, we analyzed the role of oxidation and N-acetylation as major transformation steps. PPD and its oxidative and N-acetylated derivatives were tested for their sensitizing potential in vitro using a dendritic cell (DC) activation assay and in vivo using the local lymph node assay (LLNA). PPD did not induce relevant DC activation but induced a positive LLNA response. In contrast, DC activation was obtained when PPD was chemically pre-oxidized or after air oxygen exposure. Under both conditions, the potent sensitizing PPD oxidation product Bandrowski's base was identified along with other di- and trimeric species, indicating that PPD oxidation products provide an effective immune stimulation (danger signal). In contrast mono- and diacetylated PPD did not induce DC activation or a positive LLNA response. We conclude that dermal N-acetylation of PPD competes with the formation of oxidized PPD whereas skin exposure conditions allowing auto-oxidation, as in the LLNA, provide an effective danger signal necessary to induce skin sensitization to PPD.
authors.affiliation: Procter and Gamble Co., Wella-Cosmital, Marly, Switzerland.
authors.forename: Pierre
authors.initials: P
authors.lastname: Aeby
authors.forename: Thomas
authors.initials: T
authors.lastname: Sieber
authors.forename: Heinz
authors.initials: H
authors.lastname: Beck
authors.forename: G Frank
authors.initials: GF
authors.lastname: Gerberick
authors.forename: Carsten
authors.initials: C
authors.lastname: Goebel
mesh_terms: D000107:Acetylation; D000388:Air; D000818:Animals; D004396:Coloring Agents / Q000494:pharmacology; D003470:Culture Media / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology*; D006801:Humans; D007107:Immune System; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D008954:Models, Biological; D009000:Monocytes / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010655:Phenylenediamines / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D004396:Coloring Agents; D003470:Culture Media; D010655:Phenylenediamines; D010100:Oxygen; C029728:4-phenylenediamine