Interferon-Gamma Enhances TLR3 Expression and Anti-Viral Activity in Keratinocytes

Toll-like receptors (TLRs) recognize specific microbial products in the innate immune response. TLR3, a double-stranded RNA sensor, is thought to have an important role in viral infections, but the regulation of TLR3 expression and its function in keratinocytes are not fully understood. Here we show...

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Bibliographic Details
Published in:Journal of investigative dermatology 2015-08, Vol.135 (8), p.2005-2011
Main Authors: Kajita, A.i., Morizane, Shin, Takiguchi, Tetsuya, Yamamoto, Takenobu, Yamada, Masao, Iwatsuki, Keiji
Format: Article
Language:English
Subjects:
Cells, Cultured
Chloroquine - pharmacology
Cytokines - metabolism
Drug Synergism
Herpes simplex virus
Herpesvirus 1, Human - drug effects
Humans
Immunity, Innate - drug effects
Immunity, Innate - physiology
In Vitro Techniques
Interferon-gamma - pharmacology
Keratinocytes - drug effects
Keratinocytes - metabolism
Keratinocytes - virology
Poly I-C - pharmacology
RNA, Small Interfering - pharmacology
STAT1 Transcription Factor - metabolism
Toll-Like Receptor 3 - genetics
Toll-Like Receptor 3 - metabolism
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Summary:Toll-like receptors (TLRs) recognize specific microbial products in the innate immune response. TLR3, a double-stranded RNA sensor, is thought to have an important role in viral infections, but the regulation of TLR3 expression and its function in keratinocytes are not fully understood. Here we show the Th1 cytokine IFN-γ increased the TLR3 expression via STAT1 in cultured normal human epidermal keratinocytes (NHEKs). Co-stimulation with IFN-γ and the TLR3 ligand poly (I:C) synergistically increased the expression of IFN-β, IL-6, IL-8, and human β-defensin-2 in NHEKs compared with poly (I:C) or IFN-γ alone. These synergistic inductions were significantly inhibited by an endosomal acidification inhibitor, chloroquine, and by TLR3 siRNA. Co-stimulation with IFN-γ and poly (I:C) also significantly enhanced the anti-viral activity against herpes simplex virus type-1 in NHEKs compared with poly (I:C) or IFN-γ alone. In addition to the in vitro findings, an immunohistochemical analysis revealed IFN-γ–positive cells surrounding herpetic vesicles. These findings indicate that IFN-γ might contribute to the innate immune response to cutaneous viral infections by enhancing TLR3 expression and function in keratinocytes.
ISSN:0022-202X
1523-1747
DOI:10.1038/jid.2015.125