Identification of a cell line producing high levels of TSLP: Advantages for screening of anti-allergic drugs
Identification of a cell line producing high levels of TSLP: Advantages for screening of anti-allergic drugs
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DOI：
10.1016/j.jim.2013.10.012
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发表时间：
2014-01-15
影响因子：
2.2
通讯作者：
Hirasawa, Noriyasu
中科院分区：
文献类型：
--
作者：
Segawa, Ryosuke;Yamashita, Saori;Hirasawa, Noriyasu
胸腺基质淋巴细胞生成素（TSLP）在变态反应性疾病的诱导和加重中起重要作用。这些发现表明TSLP产生的抑制剂可能是一种治疗过敏性疾病的新药。然而，进行高通量筛选这些化合物是困难的，因为目前没有合适的体外系统。在本研究中，我们证明了小鼠角质形成细胞系KCMH-1产生的TSLP量高于小鼠角质形成细胞系PAM-212、人角质形成细胞系HaCaT或支气管细胞系BEAS-2B。报告基因测定显示，KCMH-1细胞中TSLP基因的转录活性也明显高于PAM 212细胞。地塞米松和维甲酸X受体激动剂HX 600均能抑制KCMH-1细胞TSLP的产生，表明TSLP的产生是受地塞米松调节的。此外，从培养基中的KCMH-1细胞释放的TSLP的生物活性通过诱导骨髓来源的树突状细胞中的OX 40 L表达而得到证实。这些结果表明，KCMH-1可用于高通量筛选TSLP产生的抑制剂，也可作为天然TSLP的来源。(C)2013 Elsevier B. V.保留所有权利。
Thymic stromal lymphopoietin (TSLP) plays critical roles in the induction and exacerbation of allergic diseases. These findings suggest that an inhibitor of TSLP production may be a novel drug for allergic diseases. However, conducting high-throughput screening of such compounds is difficult because there is currently no appropriate in vitro system. In the present study, we demonstrated that the mouse keratinocyte cell line KCMH-1 produced higher amounts of TSLP than the mouse keratinocyte cell line PAM-212, human keratinocyte cell line HaCaT, or bronchial cell line BEAS-2B. A reporter gene assay revealed that transcriptional activity of the TSLP gene was also markedly higher in KCMH-1 than in PAM212 cells. Both dexamethasone and the retinoid X receptor agonist HX600 inhibited the production of TSLP in KCMH-1 cells, which indicated that its production could be pharmacologically regulated. Moreover, the biological activity of TSLP released from KCMH-1 cells in the medium was endorsed by the induction of OX40L expression in bone marrow-derived dendritic cells. These results indicate that KCMH-1 can be utilized in high-throughput screening of inhibitors of TSLP production and also as a source of native TSLP. (C) 2013 Elsevier B.V. All rights reserved.