Heat shock protein 90 is involved in IL-17-mediated skin inflammation following thermal stimulation
Heat shock protein 90 is involved in IL-17-mediated skin inflammation following thermal stimulation
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DOI：
10.3892/ijmm.2016.2627
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发表时间：
2016-08-01
影响因子：
5.4
通讯作者：
Woo, So-Youn
中科院分区：
文献类型：
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作者：
Kim, Bo-Kyung;Park, Minhwa;Woo, So-Youn
炎症性皮肤病的发病机制涉及免疫细胞和角质形成细胞之间的相互作用，包括辅助性T细胞17（Th 17）介导的免疫应答。几种趋化因子[趋化因子（C-X-C基序）配体（CXCL）1，CXCL 5和CXCL 8]和抗菌肽[-防御素1（BD 1），LL-37，S100 A8和S100 A9]在角质形成细胞系HaCaT中用白细胞介素（IL）-17刺激后转录上调。浴疗法，通过洗澡治疗疾病，是一种经常用于治疗炎症性皮肤病的替代疗法。浸入热矿水池中通常被认为具有化学、热、机械和免疫调节益处。我们研究了热处理对皮肤病模型中IL-17介导的炎症的影响。由于Act 1是IL-17信号传导所必需的，并且是热休克蛋白90（HSP 90）的客户蛋白，我们评估了热处理后HSP 90抑制对角质形成细胞中IL-17介导的细胞因子和抗菌肽表达的影响。我们发现，在热刺激后，在IL-17（100 ng/ml）和17-N-烯丙基氨基-17-去甲氧基格尔德霉素（17-AAG，1 μ M）的存在下，Act 1与HSP 90的结合显著增加。抗菌肽和趋化因子的表达普遍增加热处理后，Act 1敲低和17-AAG逆转这种影响。这些观察结果表明，在IL-17介导的炎症性皮肤病的进展过程中，热对角质形成细胞可能具有免疫调节作用。
The pathogenesis of inflammatory skin diseases involves interactions between immune cells and keratinocytes, including the T helper 17 (Th17)-mediated immune response. Several chemokines [chemokine (C-X-C motif) ligand (CXCL)1, CXCL5 and CXCL8] and antimicrobial peptides [-defensin 1 (BD1), LL-37, S100A8 and S100A9] were transcriptionally upregulated in the keratinocyte cell line HaCaT upon stimulation with interleukin (IL)-17. Balneotherapy, the treatment of disease by bathing, is an alternative therapy that has frequently been used for the treatment of inflammatory skin diseases. Immersion in pools of thermal mineral water is often considered to have chemical, thermal, mechanical and immunomodulatory benefits. We examined the effect of thermal treatment on IL-17-mediated inflammation in a model of skin disease. As Act1 is required for IL-17 signaling and is a client protein of heat shock protein 90 (HSP90), we evaluated the effect of HSP90 inhibition on IL-17-mediated cytokine and antimicrobial peptide expression in keratinocytes following heat treatment. We found that after thermal stimulation, Act1 binding to HSP90 was significantly increased in the presence of IL-17 (100 ng/ml) and 17-N-allylamino-17-demethoxygeldanamycin (17-AAG, 1 mu M). Antimicrobial peptide and chemokine expression generally increased after heat treatment; Act1 knockdown and 17-AAG reversed this effect. These observations demonstrate the possible immunomodulatory effect of heat on keratinocytes during the progression of IL-17-mediated inflammatory skin diseases.