• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cellular Signalling >A steroid alkaloid derivative 02F04 upregulates thymic stromal lymphopoietin expression slowly and continuously through a novel Gq/11-ROCK-ERK1/2 signaling pathway in mouse keratinocytes
【24h】

A steroid alkaloid derivative 02F04 upregulates thymic stromal lymphopoietin expression slowly and continuously through a novel Gq/11-ROCK-ERK1/2 signaling pathway in mouse keratinocytes

机译：类固醇生物碱衍生物02F04通过小鼠角质形成细胞的新GQ / 11-ROCK-ERK1 / 2信号通路缓慢且连续地将胸腺基质淋巴泛菌素表达上调

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Thymic stromal lymphopoietin (TSLP), a master switch of allergic inflammation, plays an important role in the pathogenesis of allergic diseases. Although many compounds upregulate TSLP expression in vivo or in vitro, most of them are pollutants or toxicants. In the previous study, for the first time, we found that a steroid alkaloid derivative 02F04, which has a unique skeletal structure compared with other TSLP-inducing chemicals, significantly induced TSLP production in mouse keratinocytes. However, it is not investigated thoroughly that how 02F04 produces TSLP and why. In this study, we did a detailed investigation on the inducible effect and underlying molecular mechanism of 02F04 on TSLP production. We found that the peak time of TSLP mRNA level induced by 02F04 at 48 h led to a slow and continuous TSLP production in PAM212 cells. Besides, 02F04-induced TSLP production was significantly suppressed by inhibitors of Rho-associated protein kinase (ROCK), guanine nucleotide-binding protein subunit alpha q/11 (Gq/11) and extracellular signal-regulated kinase 1/2 (ERK1/2) at not only protein but also mRNA levels, and by siRNA-mediated knockdown of Gq or G11. This suggested that ROCK, Gq/11 and ERK1/2 signaling pathways were involved in 02F04-induced TSLP production. Increase in the level of p-ERK1/2 induced by 02F04 was suppressed by both inhibitors of ROCK and Gq/11, indicating that ROCK and Gq/11 molecules were located at the upstream of ERK1/2 to regulate 02F04-induced TSLP production. Gq/11 was located at the upstream of ROCK because the specific Gq/11 inhibitor of YM-254890 significantly reduced 02F04-induced actin stress fiber formation. Taken together, 02F04 upregulates a slow and continuous TSLP production through a novel Gq/11-ROCK-ERK1/2 signaling pathway. The thorough understanding the effect and mechanism of 02F04 on TSLP production is expected to supply it as a novel TSLP-regulating compound and a potential new tool for investigating the role of TSLP in
机译：胸腺基质淋巴细胞素（TSLP），过敏性炎症的主转换，在过敏性疾病的发病机制中起重要作用。虽然许多化合物在体内或体外上调了TSLP表达，但其中大多数是污染物或毒物。在前一种研究中，我们首次发现类固醇生物碱衍生物02F04，与其他TSLP诱导化学品相比，具有独特的骨骼结构，显着诱导小鼠角质形成细胞的TSLP生产。但是，它没有彻底调查，02F04如何产生TSLP以及为什么。在本研究中，我们对02F04对TSLP生产的诱导效应和潜在分子机制进行了详细的研究。我们发现，在48小时下由02F04诱导的TSLP mRNA水平的峰值时间导致PAM212细胞中的缓慢和连续的TSLP产生。此外，通过RHO相关蛋白激酶（岩石），鸟嘌呤核苷酸结合蛋白亚基αQ/ 11（GQ / 11）和细胞外信号调节激酶1/2（ERK1 / 2）的抑制剂）不仅蛋白质，还具有mRNA水平，并通过siRNA介导的GQ或G11的敲低。这表明岩石，GQ / 11和ERK1 / 2信号传导途径涉及02F04诱导的TSLP生产。通过岩石和GQ / 11的两种抑制剂抑制02F04诱导的P-ERK1 / 2水平的增加，表明岩石和GQ / 11分子位于ERK1 / 2的上游，以调节02F04诱导的TSLP生产。 GQ / 11位于岩石上游，因为YM-254890的特定GQ / 11抑制剂显着降低了02F04诱导的肌动蛋白应激纤维形成。连合在一起，02F04通过新型GQ / 11-Rock-ERK1 / 2信号通路上调缓慢和连续的TSLP生产。彻底了解02F04对TSLP生产的效果和机制预计将作为一种新型的TSLP调节化合物和潜在的新工具，用于调查TSLP的作用

著录项

  • 来源
    《Cellular Signalling》 |2019年第2019期|共7页
  • 作者

    Weng Yan; Wang Jingwen; Yang Zhifu; Xi Miaomiao; Duan Jialin; Guo Chao; Yin Ying; Segawa Ryosuke; Moriya Takahiro; Yonezawa Takayuki; Cha Byung Yoon; Woo Je-Tae; Wen Aidong; Hirasawa Noriyasu;

  • 作者单位

    Air Force Med Univ Xijing Hosp Dept Pharm Xian 710032 Shaanxi Peoples R China;

    Air Force Med Univ Xijing Hosp Dept Pharm Xian 710032 Shaanxi Peoples R China;

    Air Force Med Univ Xijing Hosp Dept Pharm Xian 710032 Shaanxi Peoples R China;

    Air Force Med Univ Xijing Hosp Dept Pharm Xian 710032 Shaanxi Peoples R China;

    Air Force Med Univ Xijing Hosp Dept Pharm Xian 710032 Shaanxi Peoples R China;

    Air Force Med Univ Xijing Hosp Dept Pharm Xian 710032 Shaanxi Peoples R China;

    Air Force Med Univ Xijing Hosp Dept Pharm Xian 710032 Shaanxi Peoples R China;

    Tohoku Univ Grad Sch Pharmaceut Sci Lab Pharmacotherapy Life Style Related Dis Sendai Miyagi 9808578 Japan;

    Tohoku Univ Grad Sch Pharmaceut Sci Lab Pharmacotherapy Life Style Related Dis Sendai Miyagi 9808578 Japan;

    Chubu Univ Res Inst Biol Funct Kasugai Aichi 4878501 Japan;

    Chubu Univ Res Inst Biol Funct Kasugai Aichi 4878501 Japan;

    Chubu Univ Coll Biosci &

    Biotechnol Dept Biol Chem Kasugai Aichi 4878501 Japan;

    Air Force Med Univ Xijing Hosp Dept Pharm Xian 710032 Shaanxi Peoples R China;

    Tohoku Univ Grad Sch Pharmaceut Sci Lab Pharmacotherapy Life Style Related Dis Sendai Miyagi 9808578 Japan;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞形态学;
  • 关键词

    02F04; Thymic stromal lymphopoietin; Gq/11; Rho-associated protein kinase; Extracellular signal-regulated kinase 1/2;

    机译：02F04;胸腺基质淋巴泛素;GQ / 11;RHO相关蛋白激酶;细胞外信号调节激酶1/2;

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号