• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Experimental dermatology >TLR TLR 4 acts as a death receptor for ultraviolet radiation ( UVR UVR ) through IRAK IRAK ‐independent and FADD FADD ‐dependent pathway in macrophages
【24h】

TLR TLR 4 acts as a death receptor for ultraviolet radiation ( UVR UVR ) through IRAK IRAK ‐independent and FADD FADD ‐dependent pathway in macrophages

机译：TLR TLR 4通过伊拉克Irak-Independent和FADD FADD依赖于巨噬细胞的紫外线辐射（UVR UVR）的死亡受体。

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

Abstract UVR ‐induced apoptosis in cutaneous antigen presenting cells ( APC ) causes systemic immune suppression and is dependent on TLR 4/MyD88 signalling, but the apoptotic signalling pathways have not been defined. Macrophages pretreated with lipopolysaccharide ( LPS ) were unresponsive to subsequent LPS treatment, however, but were susceptible to UVR ‐induced apoptosis. Macrophage survival and apoptotic events after UVR were also unaffected by treatment with TLR 4 antagonists, a blocking IgG or a TLR 4 analog antagonist, suggesting that UVR cell death is independent of a soluble ligand. After UVR , IRAK 4 KDKI (catalytically inactive IRAK 4) and wild‐type ( WT ) macrophages show equivalent levels of survival, as measured by MTT assay, and apoptosis, as measured by cleaved caspase‐3. Furthermore, in macrophages from both mice, UVR activated caspase‐8 and PARP , while inactivating Rip3. This finding is supported by a lack of IRAK 1 degradation after UVR , compared to treatment with TLR 2 or TLR 4 agonists. UVR induced association of MyD88 with FADD , an extrinsic apoptotic pathway protein, but not IRAK 4. UVR ‐induced migration of FADD to the cell membrane of WT macrophages, but not MyD88 ?/? macrophages, was observed (confocal microscopy). Co‐immunoprecipitation using an epitope‐tagged MyD88 revealed that FADD , but not TRADD , was recruited to MyD88 within 30?minutes of UVR exposure. UVR engages TLR 4/MyD88 as a death signalling complex, rather than the classical inflammatory signalling pathway triggered by PAMP recognition of TLR 4. These studies provide the rationale for the future development of topical TLR 4 modulating therapies to interfere with this UVB ‐mediated apoptosis and the associated negative consequences of immune suppression.
机译：摘要UVR-诱导皮肤抗原呈递细胞（APC）的细胞凋亡会导致系统性免疫抑制，取决于TLR 4 / MyD88信号，但尚未定义凋亡的信号通路。然而，用脂多糖（LPS）预处理的巨噬细胞对随后的LPS治疗，但易于UVR-诱导的细胞凋亡。 UVR后巨噬细胞存活和凋亡事件也不受TLR 4拮抗剂的处理，阻断IgG或TLR 4类似物拮抗剂的影响，表明UVR细胞死亡与可溶性配体无关。 UVR后，IRAK 4 KDKI（催化活性IRAK 4）和野生型（WT）巨噬细胞显示通过MTT测定测量的等效存活率，并通过切割的Caspase-3测量。此外，在来自小鼠的巨噬细胞中，UVR活化的Caspase-8和PARP，同时灭活RIP3。与用TLR 2或TLR 4激动剂的治疗相比，这种发现得到了缺乏伊拉克1降解的支持。 UVR诱导MYD88与FADD的关联，外在凋亡途径蛋白，但不是IRAK 4. UVR诱导FADD的迁移到WT巨噬细胞的细胞膜，但不是MYD88？/？巨噬细胞被观察到（共聚焦显微镜）。使用Epitope标记的MYD88的共同免疫沉淀揭示了FADD，但不是TRADD，在30次UVR曝光的时间内招募到MyD88。 UVR将TLR 4 / MYD88作为死亡信号传播复合物，而不是由TLR 4的PAMP识别引发的经典炎症信号通路4.这些研究提供了未来局部TLR 4调节疗法的未来发展的理由，以干扰该UVB介导的细胞凋亡和免疫抑制的相关负面后果。

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