Thymic stromal lymphopoietin enhances tight-junction barrier function of human nasal epithelial cells.
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, Pam(3)Cys-Ser-(Lys)(4), and a mixture of interleukin-1beta and tumor necrosis factor-alpha. 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.
Kamekura
Ryuta
R
Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Kojima
Takashi
T
Koizumi
Jun-ichi
J
Ogasawara
Noriko
N
Kurose
Makoto
M
Go
Mitsuru
M
Harimaya
Atsushi
A
Murata
Masaki
M
Tanaka
Satoshi
S
Chiba
Hideki
H
Himi
Tetsuo
T
Sawada
Norimasa
N
D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D057167:Claudins / Q000235:genetics* / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D003713:Dendritic Cells / Q000473:pathology*; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D055666:Lipopeptides / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism; D062793:Occludin; D012221:Rhinitis, Allergic, Perennial / Q000473:pathology / Q000503:physiopathology; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation; D000094632:Thymic Stromal Lymphopoietin
D057167:Claudins; D016207:Cytokines; D053583:Interleukin-1beta; D055666:Lipopeptides; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; C508075:Pam(3)CSK(4) peptide; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D000094632:Thymic Stromal Lymphopoietin