首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >Attenuated TLR4/MAPK signaling in monocytes from patients with CRMO results in impaired IL-10 expression
【24h】

Attenuated TLR4/MAPK signaling in monocytes from patients with CRMO results in impaired IL-10 expression

机译:CRMO患者单核细胞中TLR4 / MAPK信号减弱导致IL-10表达受损

获取原文
获取原文并翻译 | 示例
           

摘要

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disorder of unknown origin. We previously demonstrated that monocytes from CRMO patients fail to express the immune-modulatory cytokine interleukin10 (IL10) in a chromatin dependent manner. Here, we demonstrate that attenuated extracellular-signal regulated kinase (ERK)1 and 2 signaling in response to TLR4 activation results in failure to induce IL-10 expression in monocytes from CRMO patients. Attenuated ERK1/2 activation results in 1) reduced levels of Sp-1, a transcription factor that induces IL-10 expression in monocytes, and 2) impaired H3S10 phosphorylation of the IL10 promoter, an activating epigenetic mark. The pro-inflammatory cytokines tumor necrosis factor (TNF)α and IL-6 are not negatively affected, resulting in an imbalance towards pro-inflammatory cytokines. Thus, impaired ERK1/2 signaling with subsequently reduced Sp-1 expression and H3S10 phosphorylation of the IL10 promoter may centrally contribute to the pathophysiology of CRMO.
机译:慢性复发性多灶性骨髓炎(CRMO)是一种来源不明的自身炎症性骨病。我们先前证明,来自CRMO患者的单核细胞不能以染色质依赖性方式表达免疫调节细胞因子白介素10(IL10)。在这里,我们证明响应TLR4激活的细胞外信号调节激酶(ERK)1和2减弱信号导致无法诱导CRMO患者单核细胞中IL-10表达。减弱的ERK1 / 2激活导致1)Sp-1(一种在单核细胞中诱导IL-10表达的转录因子)的水平降低,以及2)IL10启动子(激活的表观遗传标记)的H3S10磷酸化受损。促炎细胞因子肿瘤坏死因子(TNF)α和IL-6不受负面影响,导致促炎细胞因子失衡。因此,受损的ERK1 / 2信号传导,随后Sp-1表达降低以及IL10启动子的H3S10磷酸化可能集中地促进CRMO的病理生理。

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