ID 53018
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Author
Takiguchi, T
Yamamoto, T
Kajita, A
Ikeda, K
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)-beta through Toll-like receptor (TLR) 9. However, the effect of LL-37 on the induction of IFN-beta 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-beta 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-beta 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 up-regulated 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.
Note
This is the accepted version of the following article: FULLCITE, which has been published in final form at http://dx.doi.org/10.1111/bjd.12942
学位審査副論文
Published Date
2014-09
Publication Title
British Journal of Dermatology
Volume
volume171
Issue
issue3
Start Page
492
End Page
498
ISSN
0007-0963
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
Copyright Holders
© 2014 British Association of Dermatologists
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Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/52974
http://ousar.lib.okayama-u.ac.jp/53764