title: Impaired Tight Junctions in Atopic Dermatitis Skin and in a Skin-Equivalent Model Treated with Interleukin-17.
abstract: Tight junction (TJ) dysfunction in the stratum granulosum leads to aberrant barrier function of the stratum corneum (SC) in the epidermis. However, it is unclear whether TJs are perturbed in atopic dermatitis (AD), a representative aberrant SC-related skin disease, and whether some factors related to AD pathogenesis induce TJ dysfunction. To address these issues, we investigated the alterations of TJs in AD skin and the effects of Th2 and Th17 cytokines on TJs in a skin-equivalent model. The levels of TJ proteins were determined in the epidermis of nonlesional and lesional skin sites of AD. Western blot and immunohistochemical analyses revealed that the levels of zonula occludens 1 were decreased in the nonlesional sites of AD, and the levels of zonula occludens 1 and claudin-1 were decreased in the lesional sites relative to the levels in skin from healthy subjects. Next, we examined the effects of interleukin (IL)-4, tumor necrosis factor-α, IL-17, and IL-22 on the TJ barrier in a skin-equivalent model. Only IL-17 impaired the TJ barrier. Furthermore, we observed a defect in filaggrin monomer degradation in the IL-17-treated skin model. Thus, TJs are dysfunctional in AD, at least partly, due to the effect of IL-17, which may result in an aberrant SC barrier.
authors: Biological Science Research, Kao Corporation, Odawara, Japan.
authors: Takuo
authors: T
authors: Yuki
authors: Biological Science Research, Kao Corporation, Odawara, Japan.
authors: Megumi
authors: M
authors: Tobiishi
authors: Biological Science Research, Kao Corporation, Odawara, Japan.
authors: Ayumi
authors: A
authors: Kusaka-Kikushima
authors: Biological Science Research, Kao Corporation, Odawara, Japan.
authors: Yukiko
authors: Y
authors: Ota
authors: Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors: Yoshiki
authors: Y
authors: Tokura
mesh_terms: D002478:Cells, Cultured; D062445:Claudin-1 / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000378:metabolism / Q000473:pathology*; D000091344:Filaggrin Proteins; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D062725:Tight Junction Proteins / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D062826:Zonula Occludens-1 Protein / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D062445:Claudin-1; D000091344:Filaggrin Proteins; D020381:Interleukin-17; D015847:Interleukin-4; D007378:Interleukins; D062725:Tight Junction Proteins; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; D000097043:Interleukin-22; C000717249:FLG protein, human; C569042:TJP1 protein, human