School of Medicine, Trinity College Dublin, Trinity Biomedical Sciences Institute, Dublin, Ireland.
Front Immunol. 2021 Mar 9;12:647329. doi: 10.3389/fimmu.2021.647329. eCollection 2021.
The transcription factor Related Orphan Receptor Alpha (RORα) plays an important role in regulating circadian rhythm, inflammation, metabolism and cellular development. Herein we show that in the absence of functional RORα in mice there is reduced susceptibility to LPS-induced endotoxic shock, with selective decreases in release of pro-inflammatory cytokines. Treatment of mice with a RORα selective synthetic inhibitor also reduced the severity of LPS-induced endotoxemia. The reduction in responses in Rora deficient mice was associated with an alterations in metabolic and pro-inflammatory functions of macrophages, both peritoneal macrophages and generated bone marrow derived macrophages. Using LysM mice the reduced susceptibility to LPS was shown to be specific to expression in the macrophages. This study identifies that -mediated regulation of macrophages impacts on the pro-inflammatory responses elicited by LPS.
转录因子相关孤核受体α（RORα）在调节昼夜节律、炎症、代谢和细胞发育方面发挥着重要作用。本文研究表明，在缺乏功能性 RORα的小鼠中，脂多糖（LPS）诱导的内毒素休克的易感性降低，促炎细胞因子的释放选择性减少。用 RORα 选择性合成抑制剂治疗小鼠也可降低 LPS 诱导的内毒素血症的严重程度。Rora 缺陷型小鼠反应的减少与巨噬细胞代谢和促炎功能的改变有关，无论是腹腔巨噬细胞还是骨髓来源的巨噬细胞。使用 LysM 小鼠，表明 LPS 敏感性的降低仅限于巨噬细胞中的表达。这项研究表明，-调节的巨噬细胞影响 LPS 引发的促炎反应。
