Wy14643, an agonist for PPARα, down-regulates expression of TARC and RANTES in cultured human keratinocytes
Wy14643, an agonist for PPARα, down-regulates expression of TARC and RANTES in cultured human keratinocytes
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Wy14643 是一种 PPARα 激动剂，可下调培养的人角质形成细胞中 TARC 和 RANTES 的表达
DOI：
10.1111/exd.13245
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发表时间：
2017
影响因子：
3.6
通讯作者：
Hatano Y
中科院分区：
文献类型：
--
作者：
Zhang W;Sakai T;Fujiwara S;Hatano Y
Wy14643是一种过氧化物酶体增殖物激活受体（PPAR）α激动剂，对角质形成细胞的渗透性屏障稳态相关功能（如上调表皮分化相关分子和脂质合成）具有有益作用。本研究表明，Wy14643降低胸腺和活化相关趋化因子（TARC）的表达，并调节活化正常T细胞表达（RANTES）在单一和三维培养的人角质形成细胞。目前和以前的研究的综合数据支持这样的观点，即Wy14643可能是一种治疗剂，可能同时和直接调节特应性皮炎发病机制中的渗透屏障功能障碍和过敏性炎症。在抗微生物屏障功能方面，本研究表明，Wy14643仅在mRNA水平上调了体外培养的人角质形成细胞中的抗微生物肽人β防御素3的表达，而在蛋白水平上没有上调，这表明Wy14643可能不能直接解释已报道的体内抗微生物肽的上调。
Beneficial effects of Wy14643, an agonist for peroxisome proliferator-activated receptor (PPAR) α, on permeability barrier homeostasis-related functions of keratinocytes such as up-regulation of epidermal differentiation-related molecules and lipid synthesis, have been demonstrated. The present study demonstrated that Wy14643 reduced the expression of thymus and activationrelated chemokine (TARC) and regulated on activation normal T cell expressed (RANTES) in both single-and 3D-cultured human keratinocytes. The combined data of the present and previous studies support the notion that Wy14643 could be a therapeutic agent that might simultaneously and directly modulate permeability barrier dysfunction and allergic inflammation in the pathogenesis of atopic dermatitis. As for the anti-microbial barrier function, the present study demonstrated that Wy14643 up-regulated expression of the anti-microbial peptide, human β defensin 3, in cultured human keratinocytes only in mRNA levels but not in protein ones, suggesting that Wy14643 might not directly account for the up-regulation of the anti-microbial peptide which has been reported in vivo.