Thymic stromal lymphopoietin enhances tight-junction barrier function of human nasal epithelial cells |
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Authors: | Ryuta Kamekura Takashi Kojima Jun-ichi Koizumi Noriko Ogasawara Makoto Kurose Mitsuru Go Atsushi Harimaya Masaki Murata Satoshi Tanaka Hideki Chiba Tetsuo Himi Norimasa Sawada |
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Institution: | 1. Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo, Japan 2. Department of Pathology, Sapporo Medical University School of Medicine, South-1, West-17, Chuo-ku, Sapporo, 060-8556, Japan
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Abstract: | Epithelial-derived thymic stromal lymphopoietin (TSLP) triggers dendritic cell (DC)-mediated Th2-type inflammatory responses and is a master switch for allergic inflammatory diseases. In the present study, the expression and induction of TSLP and the effects of TSLP on the tight-junctional barrier of human nasal epithelial cells (HNECs) have been investigated in order to elucidate the role of TSLP in allergic rhinitis. We have found high expression of TSLP in the epithelium from patients with allergic rhinitis with recruitment and infiltration of DCs. In vitro, TSLP is significantly produced in HNECs after treatment with a toll-like receptor 2 (TLR2) ligand, Pam3Cys-Ser-(Lys)4, and a mixture of interleukin-1β and tumor necrosis factor-α. Treatment with TSLP rapidly enhances the barrier function of cultured HNECs, together with an increase of tight-junction proteins claudin-1, -4, -7, and occludin. The nasal-epithelial-derived TSLP thus not only activates DCs but also preserves the epithelial barrier via the upregulation of tight-junction proteins, thereby regulating antigen sensitization during the early stage of allergic rhinitis. |
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