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Dual oxidase 2 is essential for house dust mite‐induced pro‐inflammatory cytokine production in human keratinocytes
Author(s) -
Ko Eunbi,
Choi Hyun,
Park KkotNara,
Park JuYearl,
Lee Tae Ryong,
Shin Dong Wook,
Bae Yun Soo
Publication year - 2015
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.12808
Subject(s) - tlr2 , cytokine , keratinocyte , ccl20 , biology , inflammation , chemokine , microbiology and biotechnology , transfection , immunology , gene silencing , tlr4 , chemokine receptor , cell culture , biochemistry , genetics , gene
House dust mites ( HDM s) are known to trigger chronic inflammation through Toll‐like receptors ( TLR s) and their signalling cascades. In this study, we found that TLR 2 ligation by HDM s induced the activation of dual oxidase 2 ( D uox2) and nuclear factor‐κ B ( NF ‐κ B ), leading to the production of pro‐inflammatory cytokines in human keratinocytes. Stimulation of human keratinocytes with HDM s resulted in increases in interleukin‐8 ( IL ‐8) and chemokine (C–C motif) ligand 20 ( CCL 20) levels. However, pro‐inflammatory cytokine production was abolished in keratinocytes transfected with TLR 2 si RNA , indicating that HDM ‐induced cytokine production was mediated via TLR 2 signalling. We also examined the function of D uox1/2 isozymes, which are primarily expressed in keratinocytes, in HDM ‐mediated pro‐inflammatory cytokine production. Human keratinocytes transfected with control si RNA or D uox1 si RNA showed no inhibition of IL ‐8 or CCL 20 production in response to HDM s, whereas the silencing of D uox2 expression resulted in a failure to induce cytokine production. Moreover, the phosphorylation and nuclear localization of R el A /p65, a component of NF ‐κ B , were induced by HDM s in human keratinocytes. Transfection of human keratinocytes with TLR 2 si RNA or D uox2 si RNA resulted in the complete abolishment of R el A /p65 nuclear localization in response to HDM s. Taken together, these results indicate that the HDM ‐dependent TLR 2‐ D uox2 signalling axis indeed promotes NF ‐κ B activation, which induces IL ‐8 and CCL 20 production and mediates epidermal keratinocyte inflammation.