title: Cathelicidin antimicrobial peptide LL-37 augments interferon-β expression and antiviral activity induced by double-stranded RNA in keratinocytes.
abstract: BACKGROUND
  Cathelicidin antimicrobial peptide LL-37 has the capacity to kill a wide range of microbes and to modify host immunity. Recently, our group observed that the activation of keratinocytes by LL-37 and DNA greatly increases interferon (IFN)-β through Toll-like receptor (TLR)9. However, the effect of LL-37 on the induction of IFN-β through TLR3, a sensor of double-stranded (ds) RNA, in keratinocytes is not well known.
  
  
  OBJECTIVE
  To investigate whether LL-37 could affect TLR3 signalling and antiviral activity in normal human epidermal keratinocytes (NHEKs).
  
  
  METHODS
  We investigated the production of IFN-β in NHEKs stimulated with a TLR3 ligand, poly (I:C), in the presence of LL-37. To examine the effect of LL-37 and poly (I:C) on antiviral activity, a virus plaque assay using herpes simplex (HS) virus type-1 was carried out. The uptake of poly (I:C) conjugated with fluorescein isothiocyanate (FITC) into the keratinocytes was observed in the presence of LL-37. Immunostaining for TLR3 and LL-37 was performed using skin samples from HS.
  
  
  RESULTS
  LL-37 and poly (I:C) synergistically induced the expression of IFN-β in NHEKs. Furthermore, co-stimulation with LL-37 and poly (I:C) significantly decreased the viral plaque numbers compared with poly (I:C) or LL-37 alone. LL-37 enhanced the uptake of FITC-conjugated poly (I:C) into cells. Immunohistochemical analysis demonstrated that the expression of TLR3 and LL-37 is upregulated in HS lesions.
  
  
  CONCLUSIONS
  Our findings suggest that LL-37 augments the antiviral activity induced by dsRNA in keratinocytes, which may contribute to the innate immune response to cutaneous viral infections such as HS.
authors.affiliation: Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Takiguchi
authors.forename: S
authors.initials: S
authors.lastname: Morizane
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: A
authors.initials: A
authors.lastname: Kajita
authors.forename: K
authors.initials: K
authors.lastname: Ikeda
authors.forename: K
authors.initials: K
authors.lastname: Iwatsuki
mesh_terms: D023181:Antimicrobial Cationic Peptides; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D054804:Cathelicidins / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D006561:Herpes Simplex / Q000188:drug therapy* / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007369:Interferon Inducers / Q000493:pharmacokinetics / Q000494:pharmacology; D016899:Interferon-beta / Q000096:biosynthesis*; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D011070:Poly I-C / Q000493:pharmacokinetics / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D051196:Toll-Like Receptor 3 / Q000187:drug effects / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D023181:Antimicrobial Cationic Peptides; D000998:Antiviral Agents; D054804:Cathelicidins; D004338:Drug Combinations; D007369:Interferon Inducers; D012330:RNA, Double-Stranded; D051196:Toll-Like Receptor 3; D016899:Interferon-beta; D011070:Poly I-C