title: Interferon-Gamma Enhances TLR3 Expression and Anti-Viral Activity in Keratinocytes.
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.
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: A I
authors.initials: AI
authors.lastname: Kajita
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan. Electronic address: zanemori@cc.okayama-u.ac.jp.
authors.forename: Shin
authors.initials: S
authors.lastname: Morizane
authors.affiliation: Department of Plastic Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Takiguchi
authors.affiliation: Department of Dermatology, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Takenobu
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Virology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Iwatsuki
mesh_terms: D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004357:Drug Synergism; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000821:virology*; D011070:Poly I-C / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D050794:STAT1 Transcription Factor / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D034741:RNA, Small Interfering; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D007371:Interferon-gamma; D002738:Chloroquine; D011070:Poly I-C
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