...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >IL-33 mediates antigen-induced cutaneous and articular hypernociception in mice
【24h】

IL-33 mediates antigen-induced cutaneous and articular hypernociception in mice

机译：IL-33介导抗原诱导的小鼠皮肤和关节痛觉过敏

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

IL-33, a new member of the IL-1 family, signals through its receptor ST2 and induces T helper 2 (Th2) cytokine synthesis and mediates inflammatory response. We have investigated the role of IL-33 in antigen-induced hypernociception. Recombinant IL-33 induced cutaneous and articular mechanical hypernociception in a time- and dose-dependent manner. The hypernociception was inhibited by soluble (s) ST2 (a decoy receptor of IL-33), IL-1 receptor antagonist (IL-1ra), bosentan [a dual endothelin (ET)_A/ET_B receptor antagonist], clazosentan (an ET_A receptor antagonist), or indomethacin (a cyclo-oxygenase inhibitor). IL-33 induced hypernociception in IL-18~(-/-) mice but not in TNFR1~(-/-) or IFNγ~(-/-) mice. The IL-33-induced hypernociception was not affected by blocking IL-15 or sympathetic amines (guanethidine). Furthermore, methylated BSA (mBSA)-induced cutaneous and articular mechanical hypernociception depended on TNFR1 and IFNy and was blocked by sST2, IL-1ra, bosentan, clazosentan, and indomethacin. mBSA also induced significant IL-33 and ST2 mRNA expression. Importantly, we showed that mBSA induced hypernociception via the IL-33→TNFα → IL-1β →IFNγ→ ET-1 → PGE_2 signaling cascade. These results therefore demonstrate that IL-33 is a key mediator of immune inflammatory hypernociception normally associated with a Th1 type of response, revealing a hitherto unrecognized function of IL-33 in a key immune pharmacological pathway that may be amenable to therapeutic intervention.
机译：IL-1 33家族的新成员IL-33通过其受体ST2发出信号，并诱导T辅助2（Th2）细胞因子合成并介导炎症反应。我们已经研究了IL-33在抗原诱导的痛觉过敏中的作用。重组IL-33以时间和剂量依赖性方式诱导皮肤和关节机械性神经痛。高伤害感受受到可溶性ST2（IL-33的诱饵受体），IL-1受体拮抗剂（IL-1ra），波生坦[双重内皮素（ET）_A / ET_B受体拮抗剂]，克拉佐坦（ET_A）的抑制受体拮抗剂）或消炎痛（环加氧酶抑制剂）。 IL-33在IL-18〜（-/-）小鼠中引起高伤害感受，但在TNFR1〜（-/-）或IFNγ〜（-/-）小鼠中不诱发。 IL-33诱导的痛觉感受不受阻滞IL-15或交感胺（胍乙啶）的影响。此外，甲基化的牛血清白蛋白（mBSA）引起的皮肤和关节机械性痛觉过敏依赖于TNFR1和IFNγ，并被sST2，IL-1ra，波生坦，克拉佐森和吲哚美辛阻断。 mBSA还诱导了重要的IL-33和ST2 mRNA表达。重要的是，我们显示mBSA通过IL-33→TNFα→IL-1β→IFNγ→ET-1→PGE_2信号级联反应诱导了神经痛。因此，这些结果表明，IL-33是通常与Th1型反应相关的免疫炎性痛觉超敏反应的关键介体，揭示了迄今为止关键的免疫药理途径中IL-33尚未被认识的功能，该途径可能适合治疗干预。

著录项

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