Ahn Sang-Il, Lim Se Jin, Gu Gyo-Jeong, Hong Chae-Yeon, Kim Ji-Soo, Jeong Hyun Jung, Koh Kwang Oh, Mang Joo Yang, Kim Dae Young, Youn Hyung-Sun
Departments of Medical Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan 336-745, Republic of Korea.
Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan 336-745, Republic of Korea.
Int Immunopharmacol. 2015 Jan;24(1):36-41. doi: 10.1016/j.intimp.2014.10.033. Epub 2014 Nov 10.
When various pathogens invade a host, toll-like receptors (TLRs) play a significant role in recognizing the pathogen-associated molecular patterns carried by the pathogens to induce innate immune reaction, followed by acquired immunity reaction. TLRs have two downstream signaling pathways, the myeloid differential factor 88 (MyD88)-dependent and toll-interleukin-1 receptor domain-containing adapter inducing interferon-β (TRIF)-dependent pathways. To evaluate the therapeutic potential of 1-[4-fluoro-2-(2-nitrovinyl)phenyl]pyrrolidine (FPP), previously synthesized in our laboratory, its effect on signal transduction via the TLR signaling pathways was examined. FPP inhibited the activation of nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3) induced by TLR agonists, as well as inhibited the expression of cyclooxygenase-2, inducible nitric oxide synthase, and interferon inducible protein-10. FPP also inhibited the activation of NF-κB and IRF3 when induced by the overexpression of downstream signaling components of the TLRs. As a result, FPP has potential to become a new therapeutic drug for many inflammatory diseases.
当各种病原体侵入宿主时，Toll样受体（TLRs）在识别病原体携带的病原体相关分子模式以诱导先天免疫反应，随后引发获得性免疫反应中发挥重要作用。TLRs有两条下游信号通路，即髓样分化因子88（MyD88）依赖性通路和含Toll白细胞介素-1受体结构域的衔接蛋白诱导干扰素-β（TRIF）依赖性通路。为了评估我们实验室之前合成的1-[4-氟-2-（2-硝基乙烯基）苯基]吡咯烷（FPP）的治疗潜力，研究了其对通过TLR信号通路进行信号转导的影响。FPP抑制了TLR激动剂诱导的核因子-κB（NF-κB）和干扰素调节因子3（IRF3）的激活，以及环氧化酶-2、诱导型一氧化氮合酶和干扰素诱导蛋白-10的表达。当由TLRs下游信号成分的过表达诱导时，FPP也抑制了NF-κB和IRF3的激活。因此，FPP有潜力成为治疗多种炎症性疾病的新型治疗药物。
