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Thymic stromal lymphopoietin enhances tight-junction barrier function of human nasal epithelial cells

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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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Abbreviations

DAPI:

4′,6-diamidino-2-phenylindole dihydrochloride

DC:

dendritic cell

HNEC:

human nasal epithelial cell

IL:

interleukin

JAM:

junctional adhesion molecule

LCA:

leukocyte common antigen

LPS:

lipopolysaccharide

P3CSK4 :

Pam3Cys-Ser-(Lys)4

RT-PCR:

reverse transcription with polymerase chain reaction

Poly (I:C):

polyinosine-polycytidylic acid

TER:

transepithelial electrical resistance

TGF-β:

transforming growth factor-β

TNF:

tumor necrosis factor

TSLP:

thymic stromal lymphopoietin

TSLPR:

part of the functional TSLP receptor

ZO:

zonula occludens

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Acknowledgments

We are grateful to Dr. Y. Somekawa (Sapporo Hospital of Hokkaido Railway Company) and Dr. K. Asano (KKR Sapporo Medical Center Tonan Hospital) for nasal mucosal tissues and to Dr. S. Kimura and Dr. S. Yokoyama (Hokkaido Children's Hospital and Medical Center) for thymic tissues.

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Authors and Affiliations

  1. Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo, Japan

    Ryuta Kamekura, Jun-ichi Koizumi, Noriko Ogasawara, Makoto Kurose, Mitsuru Go, Atsushi Harimaya & Tetsuo Himi

  2. Department of Pathology, Sapporo Medical University School of Medicine, South-1, West-17, Chuo-ku, Sapporo, 060-8556, Japan

    Ryuta Kamekura, Takashi Kojima, Noriko Ogasawara, Masaki Murata, Satoshi Tanaka, Hideki Chiba & Norimasa Sawada

Authors
  1. Ryuta Kamekura
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  2. Takashi Kojima
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  3. Jun-ichi Koizumi
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  4. Noriko Ogasawara
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  5. Makoto Kurose
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  12. Norimasa Sawada
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Corresponding author

Correspondence to Takashi Kojima.

Additional information

This work was supported by Grants-in-Aid from the National Project “Knowledge Cluster Initiative” (2nd stage, “Sapporo Biocluster Bio-S”), by the Ministry of Education, Culture, Sports Science, and Technology, by the Ministry of Health, Labour, and Welfare of Japan, by the Akiyama Foundation, and by the Japan Science and Technology Agency.

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Fig. S1: Supplemental data 1

Immunocytochemistry for tight-junction proteins claudin-1, -4, and -7 in cultured HNECs after treatment with TSLP. Bars 20 μm

High resolution image file (TIFF 2885 kb)

Fig. S2: Supplemental data 2

Western blotting for tight-junction proteins in normal nasal mucosa and in that from patients with allergic rhinitis (CL claudin). The corresponding expression levels are shown as bar graphs. Error bars represent means±SE; n=3, **P<0.01 versus normal mucosa

High resolution image file (TIFF 1589 kb)

Fig. S3: Supplemental data 3

RT-PCR for TSLPR and IL-7Rα in human nasal mucosa (in vivo) and cultured HNECs (in vitro); M 100-bp ladder DNA marker

High resolution image file (TIFF 1059 kb)

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Kamekura, R., Kojima, T., Koizumi, Ji. et al. Thymic stromal lymphopoietin enhances tight-junction barrier function of human nasal epithelial cells. Cell Tissue Res 338, 283–293 (2009). https://doi.org/10.1007/s00441-009-0855-1

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  • DOI: https://doi.org/10.1007/s00441-009-0855-1

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