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

Journal Article · Sat Jan 01 00:00:00 EST 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2010.09.023· OSTI ID:21535201

Ohkuni, Tsuyoshi ^[1]; Kojima, Takashi ^[2]; Ogasawara, Noriko ^[1]; Masaki, Tomoyuki ^[1]; Fuchimoto, Jun ^[2]; Kamekura, Ryuta; Koizumi, Jun-ichi ^[1]; Ichimiya, Shingo; Murata, Masaki; Tanaka, Satoshi ^[2]; Himi, Tetsuo ^[1]; Sawada, Norimasa ^[2]

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1. Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo (Japan)
2. Department of Pathology, Sapporo Medical University School of Medicine, Sapporo (Japan)

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.

• OSTI ID: 21535201
• Journal Information: Toxicology and Applied Pharmacology, Vol. 250, 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.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

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