Department of Geriatric Respiratory and Critical Care, Provincial Key Laboratory of Molecular Medicine for Geriatric Disease, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Department of Intensive Care Unit, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
J Cell Physiol. 2019 Nov;234(11):19990-20001. doi: 10.1002/jcp.28596. Epub 2019 Apr 3.
NLRC5, the largest member of the Nod-like receptor (NLR) family, has been reported to play a pivotal role in regulating inflammatory responses. Recent evidence suggests that NLRC5 participates in Toll-like receptor (TLR) signaling pathways and negatively modulates nuclear factor-κB (NF-κB) activation. In this study, we investigated the interaction between NLRC5 and TLR2 in the NF-κB inflammatory signaling pathway and the involvement of NLRC5 in TLR2-mediated allergic airway inflammation. We knocked down TLR2 and NLRC5, respectively in the RAW264.7 macrophage cell line by small interfering RNA (siRNA) and then stimulated the knockdown cells with lipoteichoic acid (LTA). In comparison with the negative siRNA group, the level of NLRC5 expression was lower in the TLR2 siRNA group, with a reduction in the NF-κB-related inflammatory response. Conversely, in the NLRC5 knockdown cells, after LTA-treated the level of TLR2 expression did not change but the expression levels of both NF-κB pp65 and NLRP3 increased remarkably. Thus, we hypothesize that NLRC5 participates in the LTA-induced inflammatory signaling pathway and regulates the inflammation via TLR2/NF-κB. Similarly, in subsequent in vivo experiments, we demonstrated that the expression level of NLRC5 was significantly increased in the ovalbumin-induced allergic airway inflammation. However, this effect disappeared in TLR2-deficient (TLR2 ) mice and was accompanied by reduced levels of NF-κB expression and airway inflammation. In conclusion, NLRC5 negatively regulates LTA-induced inflammatory response via a TLR2/NF-κB pathway in macrophages and also participates in TLR2-mediated allergic airway inflammation.
NLRC5 是 Nod-like 受体（NLR）家族中最大的成员，据报道其在调节炎症反应中起着关键作用。最近的证据表明，NLRC5 参与 Toll 样受体（TLR）信号通路，并负调控核因子-κB（NF-κB）的激活。在本研究中，我们研究了 NLRC5 与 TLR2 在 NF-κB 炎症信号通路中的相互作用以及 NLRC5 在 TLR2 介导的过敏性气道炎症中的作用。我们通过小干扰 RNA（siRNA）分别敲低 RAW264.7 巨噬细胞系中的 TLR2 和 NLRC5，然后用脂磷壁酸（LTA）刺激敲低细胞。与阴性 siRNA 组相比，TLR2 siRNA 组中 NLRC5 的表达水平较低，NF-κB 相关炎症反应降低。相反，在 NLRC5 敲低细胞中，经 LTA 处理后 TLR2 的表达水平没有变化，但 NF-κB pp65 和 NLRP3 的表达水平显著增加。因此，我们假设 NLRC5 参与 LTA 诱导的炎症信号通路，并通过 TLR2/NF-κB 调节炎症。同样，在随后的体内实验中，我们证明 NLRC5 在卵清蛋白诱导的过敏性气道炎症中的表达水平显著增加。然而，这种作用在 TLR2 缺陷（TLR2 ）小鼠中消失，并且 NF-κB 表达和气道炎症水平降低。总之，NLRC5 通过 TLR2/NF-κB 通路负调控巨噬细胞中 LTA 诱导的炎症反应，并且还参与 TLR2 介导的过敏性气道炎症。
