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

Ai Kajita, Shin Morizane, Tetsuya Takiguchi, Takenobu Yamamoto, Masao Yamada, Keiji Iwatsuki

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2005-2011
Number of pages7
JournalJournal of Investigative Dermatology
Volume135
Issue number8
DOIs
Publication statusPublished - Aug 21 2015

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Poly I-C
Keratinocytes
Interferon-gamma
Virus Diseases
Innate Immunity
Defensins
Double-Stranded RNA
Acidification
Toll-Like Receptors
Chloroquine
Human Herpesvirus 1
Interleukin-8
Viruses
Small Interfering RNA
Interleukin-6
Cells
Cytokines
Ligands
Skin
polyriboinosinic-polyribocytidylic acid

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Interferon-Gamma Enhances TLR3 Expression and Anti-Viral Activity in Keratinocytes. / Kajita, Ai; Morizane, Shin; Takiguchi, Tetsuya; Yamamoto, Takenobu; Yamada, Masao; Iwatsuki, Keiji.

In: Journal of Investigative Dermatology, Vol. 135, No. 8, 21.08.2015, p. 2005-2011.

Research output: Contribution to journalArticle

Kajita, Ai ; Morizane, Shin ; Takiguchi, Tetsuya ; Yamamoto, Takenobu ; Yamada, Masao ; Iwatsuki, Keiji. / Interferon-Gamma Enhances TLR3 Expression and Anti-Viral Activity in Keratinocytes. In: Journal of Investigative Dermatology. 2015 ; Vol. 135, No. 8. pp. 2005-2011.
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