Cathelicidin antimicrobial peptide LL-37 augments interferon-ß 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)-ß through Toll-like receptor (TLR)9. However, the effect of LL-37 on the induction of IFN-ß through TLR3, a sensor of double-stranded (ds) RNA, in keratinocytes is not well known. OBJECTIVES: 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-ß in NHEKs stimulated with a TLR3 ligand, poly (IC), in the presence of LL-37. To examine the effect of LL-37 and poly (IC) on antiviral activity, a virus plaque assay using herpes simplex (HS) virus type-1 was carried out. The uptake of poly (IC) 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 (IC) synergistically induced the expression of IFN-ß in NHEKs. Furthermore, co-stimulation with LL-37 and poly (IC) significantly decreased the viral plaque numbers compared with poly (IC) or LL-37 alone. LL-37 enhanced the uptake of FITC-conjugated poly (IC) 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.