Cathelicidin antimicrobial peptide LL-37 in psoriasis enables keratinocyte reactivity against TLR9 ligands.

Cathelicidin antimicrobial peptide LL-37 in psoriasis enables keratinocyte reactivity against TLR9 ligands.
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DOI:
10.1038/jid.2011.259
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发表时间:
2012-01
影响因子:
6.5
通讯作者:
Gallo, Richard L.
Gallo, Richard L.
中科院分区:
医学1区
文献类型:
--
作者:
Morizane, Shin;Yamasaki, Kenshi;Muehleisen, Beda;Kotol, Paul F.;Murakami, Masamoto;Aoyama, Yumi;Iwatsuki, Keiji;Hata, Tissa;Gallo, Richard L.

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在这里,我们表明,在银屑病皮损皮肤角质形成细胞表达增加Toll样受体(TLR)9,类似地定位与表达升高的抗菌肽LL-37。在培养中,暴露于LL-37的正常人角质形成细胞增加TLR9表达。此外,当角质形成细胞暴露于LL-37并随后用TLR9配体如CpG或基因组DNA处理时,角质形成细胞大大增加了I型干扰素的产生。这种反应模拟了银肩病皮损表皮中的观察结果,因为银肩病皮损中的角质形成细胞比缺乏LL-37的正常皮肤产生更大量的干扰素-β。角质形成细胞中I型干扰素的诱导机制依赖于TLR9的表达,但不依赖于DNA-LL-37复合物。这些发现表明,角质形成细胞识别和响应DNA,并能积极参与有助于银屑病的免疫环境。
Here we show that keratinocytes in psoriatic lesional skin express increased Toll-like receptor (TLR) 9 that similarly localizes with elevated expression of the cathelicidin antimicrobial peptide LL-37. In culture, normal human keratinocytes exposed to LL-37 increased TLR9 expression. Furthermore, when keratinocytes were exposed to LL-37 and subsequently treated with TLR9 ligands such as CpG or genomic DNA, keratinocytes greatly increased production of type I interferons. This response mimicked observations in the epidermis of psoriatic lesional skin as keratinocytes in psoriatic lesions produce greater amounts of interferon-β than normal skin lacking LL-37. The mechanism for induction of type I interferons in keratinocytes was dependent on TLR9 expression but not on a DNA-LL-37 complex. These findings suggest that keratinocytes recognize and respond to DNA and can actively participate in contributing to the immunological environment that characterizes psoriasis.
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