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Title: Poly(I:C) reduces expression of JAM-A and induces secretion of IL-8 and TNF-{alpha} via distinct NF-{kappa}B pathways in human nasal epithelial cells

Abstract

Human nasal epithelium is an important physical barrier and innate immune defense protecting against inhaled substances and pathogens. Toll-like receptor (TLR) signaling, which plays a key role in the innate immune response, has not been well characterized in human nasal epithelial cells (HNECs), including the epithelial tight junctional barrier. In the present study, mRNAs of TLR1-10 were detected in hTERT-transfected HNECs, which can be used as an indispensable and stable model of normal HNECs, similar to primary cultured HNECs. To investigate the changes of tight junction proteins and the signal transduction pathways via TLRs in HNECs in vitro, hTERT-transfected HNECs were treated with TLR2 ligand P{sub 3}CSK{sub 4}, TLR3 ligand poly(I:C), TLR4 ligand LPS, TLR7/8 ligand CL097, TLR8 ligand ssRNA40/LyoVec, and TLR9 ligand ODN2006. In hTERT-transfected HNECs, treatment with poly(I:C) significantly reduced expression of the tight junction protein JAM-A and induced secretion of proinflammatory cytokines IL-8 and TNF-{alpha}. Both the reduction of JAM-A expression and the induction of secretion of IL-8 and TNF-{alpha} after treatment with poly(I:C) were modulated by distinct signal transduction pathways via EGFR, PI3K, and p38 MAPK and finally regulated by a TLR3-mediated NF-{kappa}B pathway. The control of TLR3-mediated signaling pathways in HNECs may be important notmore » only in infection by viral dsRNA but also in autoimmune diseases caused by endogenous dsRNA released from necrotic cells.« less

Authors:
 [1];  [2];  [1];  [1];  [2]; ;  [1]; ; ;  [2];  [1];  [2]
  1. Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo (Japan)
  2. Department of Pathology, Sapporo Medical University School of Medicine, Sapporo (Japan)
Publication Date:
OSTI Identifier:
21535201
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 250; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2010.09.023; PII: S0041-008X(10)00365-0; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; DISEASES; HUMAN POPULATIONS; IN VITRO; LIGANDS; LYMPHOKINES; NOSE; RECEPTORS; SIGNALS; BODY; FACE; GROWTH FACTORS; HEAD; MEMBRANE PROTEINS; MITOGENS; ORGANIC COMPOUNDS; POPULATIONS; PROTEINS; RESPIRATORY SYSTEM

Citation Formats

Ohkuni, Tsuyoshi, Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Kojima, Takashi, Ogasawara, Noriko, Masaki, Tomoyuki, Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Fuchimoto, Jun, Kamekura, Ryuta, Koizumi, Jun-ichi, Ichimiya, Shingo, Murata, Masaki, Tanaka, Satoshi, Himi, Tetsuo, and Sawada, Norimasa. Poly(I:C) reduces expression of JAM-A and induces secretion of IL-8 and TNF-{alpha} via distinct NF-{kappa}B pathways in human nasal epithelial cells. United States: N. p., 2011. Web. doi:10.1016/j.taap.2010.09.023.
Ohkuni, Tsuyoshi, Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Kojima, Takashi, Ogasawara, Noriko, Masaki, Tomoyuki, Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Fuchimoto, Jun, Kamekura, Ryuta, Koizumi, Jun-ichi, Ichimiya, Shingo, Murata, Masaki, Tanaka, Satoshi, Himi, Tetsuo, & Sawada, Norimasa. Poly(I:C) reduces expression of JAM-A and induces secretion of IL-8 and TNF-{alpha} via distinct NF-{kappa}B pathways in human nasal epithelial cells. United States. https://doi.org/10.1016/j.taap.2010.09.023
Ohkuni, Tsuyoshi, Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Kojima, Takashi, Ogasawara, Noriko, Masaki, Tomoyuki, Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Fuchimoto, Jun, Kamekura, Ryuta, Koizumi, Jun-ichi, Ichimiya, Shingo, Murata, Masaki, Tanaka, Satoshi, Himi, Tetsuo, and Sawada, Norimasa. 2011. "Poly(I:C) reduces expression of JAM-A and induces secretion of IL-8 and TNF-{alpha} via distinct NF-{kappa}B pathways in human nasal epithelial cells". United States. https://doi.org/10.1016/j.taap.2010.09.023.
@article{osti_21535201,
title = {Poly(I:C) reduces expression of JAM-A and induces secretion of IL-8 and TNF-{alpha} via distinct NF-{kappa}B pathways in human nasal epithelial cells},
author = {Ohkuni, Tsuyoshi and Department of Pathology, Sapporo Medical University School of Medicine, Sapporo and Kojima, Takashi and Ogasawara, Noriko and Masaki, Tomoyuki and Department of Pathology, Sapporo Medical University School of Medicine, Sapporo and Fuchimoto, Jun and Kamekura, Ryuta and Koizumi, Jun-ichi and Ichimiya, Shingo and Murata, Masaki and Tanaka, Satoshi and Himi, Tetsuo and Sawada, Norimasa},
abstractNote = {Human nasal epithelium is an important physical barrier and innate immune defense protecting against inhaled substances and pathogens. Toll-like receptor (TLR) signaling, which plays a key role in the innate immune response, has not been well characterized in human nasal epithelial cells (HNECs), including the epithelial tight junctional barrier. In the present study, mRNAs of TLR1-10 were detected in hTERT-transfected HNECs, which can be used as an indispensable and stable model of normal HNECs, similar to primary cultured HNECs. To investigate the changes of tight junction proteins and the signal transduction pathways via TLRs in HNECs in vitro, hTERT-transfected HNECs were treated with TLR2 ligand P{sub 3}CSK{sub 4}, TLR3 ligand poly(I:C), TLR4 ligand LPS, TLR7/8 ligand CL097, TLR8 ligand ssRNA40/LyoVec, and TLR9 ligand ODN2006. In hTERT-transfected HNECs, treatment with poly(I:C) significantly reduced expression of the tight junction protein JAM-A and induced secretion of proinflammatory cytokines IL-8 and TNF-{alpha}. Both the reduction of JAM-A expression and the induction of secretion of IL-8 and TNF-{alpha} after treatment with poly(I:C) were modulated by distinct signal transduction pathways via EGFR, PI3K, and p38 MAPK and finally regulated by a TLR3-mediated NF-{kappa}B pathway. The control of TLR3-mediated signaling pathways in HNECs may be important not only in infection by viral dsRNA but also in autoimmune diseases caused by endogenous dsRNA released from necrotic cells.},
doi = {10.1016/j.taap.2010.09.023},
url = {https://www.osti.gov/biblio/21535201}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 250,
place = {United States},
year = {Sat Jan 01 00:00:00 EST 2011},
month = {Sat Jan 01 00:00:00 EST 2011}
}