Mitogen- and stress-activated protein kinase 2 and cyclic AMP response element binding protein are activated in lesional psoriatic epidermis
Mitogen- and stress-activated protein kinase 2 and cyclic AMP response element binding protein are activated in lesional psoriatic epidermis
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DOI：
10.1038/sj.jid.5700821
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发表时间：
2007-08-01
影响因子：
6.5
通讯作者：
Iversen, Lars
中科院分区：
文献类型：
--
作者：
Funding, Anne T.;Johansen, Claus;Iversen, Lars
p38 丝裂原激活蛋白激酶 (MAPK) 的活性在银屑病皮损皮肤中增加，支持这些激酶在银屑病发病机制中可能发挥的作用。最近，银屑病表皮中下游靶丝裂原和应激激活蛋白激酶 1 (MSK1) 的局部激活增加。本研究的目的是研究银屑病皮肤和培养的正常人角质形成细胞中的 MSK2 和转录因子环磷酸腺苷反应元件结合蛋白 (CREB)。在病变银屑病皮肤中，磷酸印迹证明 MSK2 (Ser-196) 和 CREB (Ser-133) 激活显着增加。磷酸化 MSK2 (Ser-196) 的免疫荧光染色显示表皮中与磷酸化 MSK1 (Thr 581) 共定位。用茴香霉素和 IL-1 beta 刺激的角质形成细胞培养物显示 MSK2 (Ser-196) 和 CREB (Ser133) 磷酸化增加。这种激活在与 p38 抑制剂预孵育期间被消除。与 MSK1 和 MSK2 单转染细胞相比，用小干扰 RNA 转染的角质形成细胞在 MSK1/2 双转染细胞中显示出更强烈的 CREB 磷酸化降低。这项研究首次证明了 MSK2 在角质形成细胞中的表达以及皮损银屑病皮肤中 MSK2 和 CREB 激活的增加。我们的结果表明p38-MAPK/MSK1/MSK2和CREB信号通路可能在银屑病的发病机制中发挥作用。
The activity of the p38 mitogen-activated protein kinases (MAPKs) is increased in lesional psoriatic skin, supporting a possible role of these kinases in the pathogenesis of psoriasis. Recently, increased focal activation of the downstream target mitogen- and stress-activated protein kinase 1 (MSK1) was demonstrated in psoriatic epidermis. The purpose of this study is to investigate MSK2 and the transcription factor cyclic adenosine monophosphate response element-binding protein (CREB) in psoriatic skin and in cultured normal human keratinocytes. In lesional psoriatic skin, significantly increased MSK2 (Ser-196) and CREB (Ser-133) activation was demonstrated by phospho blotting. Immunofluorescence staining of phosphorylated MSK2 (Ser-196) revealed colocalization with phosphorylated MSK1 (Thr 581) in the epidermis. Keratinocyte cultures stimulated with anisomycin and IL-1 beta showed increased MSK2 (Ser-196) and CREB (Ser133) phosphorylation. Such activation was abolished during preincubation with a p38 inhibitor. Keratinocytes transfected with small interfering RNA showed a stronger decrease in CREB phosphorylation in MSK1/2 double-transfected cells than in MSK1 and MSK2 single-transfected cells. This study demonstrate for the first time the expression of MSK2 in keratinocytes and increased MSK2 and CREB activation in lesional psoriatic skin. Our results indicate that the p38-MAPK/ MSK1/MSK2 and CREB signalling pathway may play a role in the pathogenesis of psoriasis.