Skin Sensitization to Fluorescein Isothiocyanate Is Enhanced by Butyl Paraben in a Mouse Model

• Published in: Biological & pharmaceutical bulletin 2018/12/01, Vol.41(12), pp.1853-1858
• Main Authors: Matsuoka, Takeshi, Endo, Yukina, Kurohane, Kohta, Imai, Yasuyuki
• Format: Article
• Language: English
• Subjects: Acetone; adjuvant; Animals; Ankyrins; butyl paraben; CD11c antigen; Chemicals; CHO Cells; Comparative studies; Contact dermatitis; contact hypersensitivity; Cosmetics; Cricetinae; Cricetulus; Dendritic cells; Dermatitis, Contact - metabolism; Dermatitis, Contact - pathology; Dextrans - toxicity; dibutyl phthalate; Disease Models, Animal; Dose-Response Relationship, Drug; Esters; Female; Fluorescein; Fluorescein isothiocyanate; Fluorescein-5-isothiocyanate - analogs & derivatives; Fluorescein-5-isothiocyanate - toxicity; Hypersensitivity; Lymph; Lymph nodes; Lymphatic system; Mice; Mice, Inbred BALB C; mouse; n-Butyl phthalate; Parabens - toxicity; Phthalate esters; Preservatives; Sensory neurons; Skin; Trafficking; transient receptor potential ankyrin 1; Transient receptor potential proteins
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b18-00584

Contact hypersensitivity (CHS) to preservatives is receiving increased attention. Parabens are widely used in foods, pharmaceutics and cosmetics as preservatives. The skin sensitizing activity of parabens remains controversial but a few investigations have been made as to whether parabens could facilitate sensitization to other chemicals. We have shown that di-n-butyl phthalate (DBP), a phthalate ester, has an adjuvant effect in a fluorescein isothiocyanate (FITC)-induced CHS mouse model. We have also demonstrated that DBP activates transient receptor potential ankyrin 1 (TRPA1) cation channels expressed on sensory neurons. Comparative studies of phthalate esters revealed that TRPA1 agonistic activity and the adjuvant effect on FITC-CHS coincide. Here we focused on two commonly used parabens, butyl paraben (BP) and ethyl paraben (EP), as to their adjuvant effects. BALB/c mice were epicutneously sensitized with FITC in acetone in the presence or absence of a paraben. Sensitization to FITC was evaluated as the ear-swelling response after FITC challenge. BP but not EP enhanced skin sensitization to FITC, but the effect of BP was much weaker than that of DBP. Mechanistically, BP enhanced the trafficking of FITC-presenting CD11c+ dendritic cells (DCs) from the skin to draining lymph nodes as well as cytokine production by draining lymph nodes. When the TRPA1 agonistic activity was measured with a cell line expressing TRPA1, BP exhibited higher activity than EP. The present study provides direct in vivo evidence that BP causes sensitization to other chemicals by means of a mouse FITC-CHS model.