Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan 31538, Republic of Korea.
Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan 31538, Republic of Korea.
Int Immunopharmacol. 2018 Nov;64:1-9. doi: 10.1016/j.intimp.2018.08.018. Epub 2018 Aug 21.
Toll-like receptors (TLRs) play a crucial role in the induction of innate immune response against bacterial and viral infections. TLRs induce downstream signaling via MyD88- and TRIF-dependent pathways. Cardamonin is a naturally occurring chalcone from Alpinia species exhibiting anti-inflammatory effects. However, the principal molecular mechanisms remain unclear. The objective of this study was to investigate the role of cardamonin in TLR signaling pathways. Cardamonin inhibited NF-κB activation as well as COX-2 expression induced by TLR agonists. Cardamonin inhibited the activation of IRF3 and the expression of interferon-inducible protein-10 (IP-10) induced by TLR3 or TLR4 agonists. Cardamonin also inhibited ligand-independent NF-κB activation overexpressed by MyD88, IKKβ, or p65 and IRF3 activation overexpressed by TRIF, TBK1, or IRF3. However, cardamonin had no effect on TBK1 kinase activity in vitro. These results suggest that cardamonin modulates both the MyD88- and TRIF-dependent pathways of TLRs and represents a potentially new anti-inflammatory candidate.
Toll 样受体 (TLRs) 在诱导针对细菌和病毒感染的固有免疫反应中发挥着至关重要的作用。TLRs 通过 MyD88 和 TRIF 依赖性途径诱导下游信号转导。小豆蔻明是一种来自姜科植物的天然查尔酮，具有抗炎作用。然而，主要的分子机制尚不清楚。本研究的目的是研究小豆蔻明在 TLR 信号通路中的作用。小豆蔻明抑制 TLR 激动剂诱导的 NF-κB 激活和 COX-2 表达。小豆蔻明抑制 TLR3 或 TLR4 激动剂诱导的 IRF3 激活和干扰素诱导蛋白-10 (IP-10) 的表达。小豆蔻明还抑制由 MyD88、IKKβ 或 p65 过表达的配体非依赖性 NF-κB 激活以及由 TRIF、TBK1 或 IRF3 过表达的 IRF3 激活。然而，小豆蔻明在体外对 TBK1 激酶活性没有影响。这些结果表明，小豆蔻明调节 TLR 的 MyD88 和 TRIF 依赖性途径，代表一种潜在的新型抗炎候选物。
