title: Titanium dioxide nanoparticles aggravate atopic dermatitis-like skin lesions in NC/Nga mice.
abstract: Titanium dioxide (TiO(2)) nanoparticles are produced abundantly and used ubiquitously in various cosmetic products. However, it remains to be determined whether transdermal exposure to TiO(2) nanoparticles affects atopic dermatitis (AD), which has been increasing in developed countries. We investigated the effects of different sized TiO(2) nanoparticles on AD-like skin lesions induced to mite allergen in NC/Nga mice assumed to show skin barrier dysfunction/defect. Male mice were injected intradermally with TiO(2) nanoparticles of three sizes (15, 50, or 100 nm) and/or mite allergen into their right ears. We evaluated clinical scores, ear thickening, histological findings and the protein expression of T helper (Th) 1 and Th2 cytokines in the ear, and the levels of Ig and histamine in serum. TiO(2) nanoparticles aggravated AD-like skin lesions related to mite allergen in NC/ Nga mice. The enhancing effects are paralleled by the overproduction of IL-4 in the skin, the levels of total IgE and histamine in serum regarding the overall trend. In contrast, TiO(2) nanoparticles decreased the local expression of IFN-gamma in the presence of allergen. Additionally, TiO(2) nanoparticles alone significantly increased histamine levels in serum and IL-13 expression in the ear. However, different effects related to the size differences of TiO(2) nanoparticles were not observed. In conclusion, exposure to TiO(2) nanoparticles under skin barrier dysfunction/defect can exacerbate AD symptoms through Th2-biased immune responses. Furthermore, TiO(2) nanoparticles can play a significant role in the initiation and/or progression of skin diseases following the barrier dysfunction/defect by histamine release even in the absence of allergen.
authors.affiliation: Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506, Japan. yanagi@nies.go.jp
authors.forename: Rie
authors.initials: R
authors.lastname: Yanagisawa
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Takano
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Inoue
authors.forename: Eiko
authors.initials: E
authors.lastname: Koike
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kamachi
authors.forename: Kaori
authors.initials: K
authors.lastname: Sadakane
authors.forename: Takamichi
authors.initials: T
authors.lastname: Ichinose
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000097:blood / Q000473:pathology*; D004423:Ear / Q000473:pathology; D006632:Histamine / Q000097:blood; D007136:Immunoglobulins / Q000097:blood; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000009:adverse effects*; D011506:Proteins / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000473:pathology*; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D014025:Titanium / Q000009:adverse effects*
chemical_list: D016207:Cytokines; D007136:Immunoglobulins; D018836:Inflammation Mediators; D011506:Proteins; C009495:titanium dioxide; D006632:Histamine; D014025:Titanium