Premium
Epidermal keratinocytes sense ds RNA via the NLRP 3 inflammasome, mediating interleukin ( IL )‐1β and IL ‐18 release
Author(s) -
Dai Xiuju,
Tohyama Mikiko,
Murakami Masamoto,
Sayama Koji
Publication year - 2017
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13334
Subject(s) - inflammasome , caspase 1 , innate immune system , pyrin domain , pattern recognition receptor , biology , keratinocyte , transfection , rna , sense (electronics) , microbiology and biotechnology , chemistry , receptor , immunology , immune system , biochemistry , in vitro , gene
Skin epidermis, in addition to its barrier function, is able to actively sense harmful pathogens using pattern recognition receptors. In immune cells, the nucleotide‐binding oligomerization domain, leucine‐rich repeat and pyrin domain containing 3 ( NLRP 3) inflammasome can mediate innate immunity against viral infection via a mechanism involving viral ds RNA recognition. Epidermal keratinocytes express NLRP 3 inflammasome, which can sense contact sensitizers and mite allergens, leading to pro‐interleukin ( IL )‐1β and pro‐ IL ‐18 cleavage into their active forms. Skin often faces viral infection. However, it is unknown whether viral ds RNA can be detected by the keratinocyte NLRP 3 inflammasome. We transfected polyinosinic:polycytidylic acid (poly I:C), a synthetic viral ds RNA analogue, into cultured primary human keratinocytes at the aid of Lipofectamine 2000, and found that transfected poly I:C activated caspase‐1 and induced caspase‐1‐dependent release of IL ‐1β and IL ‐18, which were suppressed on transfection with NLRP 3 si RNA . The activation of keratinocyte NLRP 3 inflammasome by transfected poly I:C was dependent on ds RNA ‐induced protein kinase ( PKR ) activation, and priming with type I interferons upregulated NLRP 3 inflammasome activation through promoting PKR activation in poly I:C‐transfected keratinocytes. In conclusion, the NLRP 3 inflammasome can act as a sensor of ds RNA in epidermal keratinocytes, which may be important in both skin innate immune defense against viral infection and skin inflammation.