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Dual oxidase 2 is essential for house dust mite-induced pro-inflammatory cytokine production in human keratinocytes

Title
Dual oxidase 2 is essential for house dust mite-induced pro-inflammatory cytokine production in human keratinocytes
Authors
Ko, EunbiChoi, HyunPark, Kkot-NaraPark, Ju-YearlLee, Tae RyongShin, Dong WookBae, Yun Soo
Ewha Authors
배윤수
SCOPUS Author ID
배윤수scopus
Issue Date
2015
Journal Title
EXPERIMENTAL DERMATOLOGY
ISSN
0906-6705JCR Link1600-0625JCR Link
Citation
vol. 24, no. 12, pp. 936 - 941
Keywords
dual oxidase 2house dust mitenuclear factor-Breactive oxygen speciesToll-like receptors
Publisher
WILEY-BLACKWELL
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
House dust mites (HDMs) are known to trigger chronic inflammation through Toll-like receptors (TLRs) and their signalling cascades. In this study, we found that TLR2 ligation by HDMs induced the activation of dual oxidase 2 (Duox2) and nuclear factor-B (NF-B), leading to the production of pro-inflammatory cytokines in human keratinocytes. Stimulation of human keratinocytes with HDMs resulted in increases in interleukin-8 (IL-8) and chemokine (C-C motif) ligand 20 (CCL20) levels. However, pro-inflammatory cytokine production was abolished in keratinocytes transfected with TLR2 siRNA, indicating that HDM-induced cytokine production was mediated via TLR2 signalling. We also examined the function of Duox1/2 isozymes, which are primarily expressed in keratinocytes, in HDM-mediated pro-inflammatory cytokine production. Human keratinocytes transfected with control siRNA or Duox1 siRNA showed no inhibition of IL-8 or CCL20 production in response to HDMs, whereas the silencing of Duox2 expression resulted in a failure to induce cytokine production. Moreover, the phosphorylation and nuclear localization of RelA/p65, a component of NF-B, were induced by HDMs in human keratinocytes. Transfection of human keratinocytes with TLR2 siRNA or Duox2 siRNA resulted in the complete abolishment of RelA/p65 nuclear localization in response to HDMs. Taken together, these results indicate that the HDM-dependent TLR2-Duox2 signalling axis indeed promotes NF-B activation, which induces IL-8 and CCL20 production and mediates epidermal keratinocyte inflammation.
DOI
10.1111/exd.12808
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자연과학대학 > 생명과학전공 > Journal papers
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