title: Characterization of skin inflammation induced by repeated exposure of toluene, xylene, and formaldehyde in mice.
abstract: Volatile organic compounds (VOCs) are considered the main cause of sick building syndrome and they are likely to irritate the skin, eyes, and mucous membrane; however, the toxic threshold and the mechanisms of cutaneous reaction induced by long-time VOC exposure have not been clarified. In the present study, we investigated the effect of repeated painting of VOCs onto mouse skin. Various concentrations of toluene, xylene, and formaldehyde (FA) were applied once a week for 5 weeks. While FA solution (2-10%) induced remarkable ear swelling and caused evident infiltration of inflammatory cells, high concentrations of toluene and xylene (50 or 100%) evoked mild ear swelling and marginal inflammatory cell invasion. In addition, FA exposure markedly increased the expression of interleukin-4 (IL-4), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and transient receptor potential vanilloid-1 (TRPV-1) mRNAs in the ears and IL-4 and NT-3 mRNAs in the cervical lymph nodes. Furthermore, capsazepine, a TRPV-1 antagonist, significantly suppressed ear swelling caused by repeated painting of 5% FA. These findings demonstrate that FA has more potent irritancy against skin than toluene or xylene and suggest that the Th2 response, neurotrophins and TRPV-1 play important roles in FA-induced skin inflammation.
authors.affiliation: Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Asaka
authors.initials: A
authors.lastname: Saito
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Haruki
authors.initials: H
authors.lastname: Usuda
authors.forename: Tomonori
authors.initials: T
authors.lastname: Shibata
authors.forename: Sayaka
authors.initials: S
authors.lastname: Higashi
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Yamashita
authors.forename: Naoki
authors.initials: N
authors.lastname: Inagaki
authors.forename: Hiroichi
authors.initials: H
authors.lastname: Nagai
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D003875:Drug Eruptions / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005557:Formaldehyde / Q000633:toxicity*; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D020933:Neurotrophin 3 / Q000235:genetics / Q000378:metabolism; D010031:Otitis / Q000139:chemically induced / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism; D014050:Toluene / Q000633:toxicity*; D014992:Xylenes / Q000633:toxicity*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D020933:Neurotrophin 3; D012333:RNA, Messenger; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D014992:Xylenes; D005557:Formaldehyde; D015847:Interleukin-4; D014050:Toluene