Thymic stromal lymphopoietin induces tight junction protein claudin-7 via NF-kappaB in dendritic cells.
Epithelial-derived thymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine that triggers dendritic cell (DC)-mediated Th2-type inflammatory responses. The activated DCs can penetrate the epithelium to directly take up antigen without compromising the barrier function. Although it is reported that DCs express tight junction molecules and can establish tight junction-like structures with adjacent epithelial cells to preserve the epithelial barrier, the regulation of expression of tight junction molecules in DCs remains unknown. In the present study, to investigate the mechanical regulation of expression of tight junction molecules in DCs, XS52 DCs that was a long-term DC line established from the epidermis of a newborn BALB/c mouse, were treated with TSLP or toll-like receptor (TLR) ligands. In XS52 cells, tight junction molecules claudin-1, -3, -4, -6, -7, -8, and occludin were detected. mRNA expression of TSLP receptor and all these tight junction molecules was significantly increased in activated XS52 cells after treatment with TSLP. In addition, expression of claudin-7 protein was increased in dose- and time-dependent manner. In XS52 cells, which express TLR2, TLR3, TLR4, and TLR7, but not TLR9, expression of claudin-7 protein was also increased after treatment with ligands of TLR2, TLR4 or TLR7/8, Pam3Cys-Ser-(Lys)4, LPS, or CL097. The NF-kappaB inhibitor IMD-0354 prevented upregulation of claudin-7 after treatment with TSLP or TLR ligands. These findings indicate that TSLP induces expression of tight junction protein claudin-7 in DCs via NF-kappaB as well as via TLRs and may control tight junctions of DCs to preserve the epithelial barrier during allergic inflammation.
Kamekura
Ryuta
R
Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Kojima
Takashi
T
Takashima
Akira
A
Koizumi
Jun-ichi
J
Ogasawara
Noriko
N
Go
Mitsuru
M
Takano
Ken-ichi
K
Murata
Masaki
M
Tanaka
Satoshi
S
Ichimiya
Shingo
S
Himi
Tetsuo
T
Sawada
Norimasa
N
D000818:Animals; D002478:Cells, Cultured; D057167:Claudins; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism*; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019108:Tight Junctions / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
D057167:Claudins; C507360:Cldn7 protein, mouse; D016207:Cytokines; D008024:Ligands; D008565:Membrane Proteins; D016328:NF-kappa B; D051193:Toll-Like Receptors; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse