title: The plasticizer dibutyl phthalate (DBP) potentiates chemical allergen-induced THP-1 activation.
abstract: Recent studies suggest that phthalates may have a role in the development of allergic diseases, probably due to an adjuvant effect. The present study aimed to investigate the possible adjuvant effect of dibutyl phthalate (DBP) in two in vitro models of contact-allergen induced cell activation, namely the NCTC 2544 IL-18 assay and the THP-1 activation assay. Results show no adjuvant effect in the human keratinocyte cell line NCTC 2544, indicated by lack of increase in interleukin 18 (IL-18) production after exposure to p-Phenylenediamine (PPD) in association with DBP. On the contrary, increased upregulation of CD86 and interleukin 8 (IL-8) production were observed in THP-1 cells exposed to combinations of citral (Cit) or imidazolidinyl urea (IMZ) with DBP, indicative of an adjuvant effect. Additionally, higher production of reactive oxygen species (ROS) in THP-1 cells treated with DBP associated to Cit supports that oxidative stress could be part of the molecular mechanism of the observed adjuvant effect. In conclusion, we demonstrate that DBP presents in vitro an adjuvant effect for immune stimulation in dendritic cells but not in keratinocytes. Future studies are necessary to elucidate the precise mechanism underlying the adjuvant effect of DBP in vitro and in vivo.
authors: Department of Pharmacology, Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil. Electronic address: analourenco@ufpr.br.
authors: A C S
authors: AC
authors: Lourenço
authors: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
authors: V
authors: V
authors: Galbiati
authors: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
authors: D
authors: D
authors: Corti
authors: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
authors: A
authors: A
authors: Papale
authors: Department of Pharmacology, Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil.
authors: A J
authors: AJ
authors: Martino-Andrade
authors: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
authors: E
authors: E
authors: Corsini
mesh_terms: D000485:Allergens / Q000633:toxicity*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003993:Dibutyl Phthalate / Q000633:toxicity*; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species
chemical_list: D000485:Allergens; D016207:Cytokines; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D003993:Dibutyl Phthalate
keywords: Adjuvant effect; Contact dermatitis; Dendritic cells; Dibutyl phthalate; In vitro toxicology; Keratinocytes