Suppression of TLRs signaling pathways by 1-[5-methoxy-2-(2-nitrovinyl)phenyl]pyrrolidine

被引:1
作者
Ahn, Sang-Il [1 ]
Kim, Ji-Soo [1 ]
Shin, Hyeon-Myeong [2 ]
Kim, Ah-Yeon [2 ]
Gu, Gyo-Jeong [1 ]
Shim, Hyun-Jin [2 ]
Kim, Yeon Joo [3 ]
Koh, Kwang Oh. [3 ]
Mang, Joo Yang [3 ]
Kim, Dae Young [3 ]
Youn, Hyung-Sun [1 ,2 ]
机构
[1] Soonchunhyang Univ, Coll Med Sci, Dept Med Sci, Chungnam 336745, Asan, South Korea
[2] Soonchunhyang Univ, Coll Med Sci, Dept Biomed Lab Sci, Chungnam 336745, Asan, South Korea
[3] Soonchunhyang Univ, Coll Nat Sci, Dept Chem, Chungnam 336745, South Korea
关键词
1-[5-methoxy-2-(2-nitrovinyl)phenyl]pyrrolidine; MyD88; Nuclear factor-kappa B; Toll-like receptor; TRIF; TOLL-LIKE RECEPTORS; NF-KAPPA-B; REGULATORY FACTOR-3; LIPOPOLYSACCHARIDE; ACTIVATION; TRANSCRIPTION; EXPRESSION; GENE; HOMODIMERIZATION; INDUCTION;
D O I
10.1016/j.intimp.2016.03.042
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Toll-like receptors (TLRs) play significant roles in recognizing the pathogen-associated molecular patterns that induce innate immunity, and subsequently, acquired immunity. In general, TLRs have two downstream signaling pathways, the myeloid differential factor 88 (MyD88)-dependent and toll-interleukin-1 receptor domain-containing adapter-inducing interferon-beta (TRIF)-dependent pathways, which lead to the activation of nuclear factor-kappa B (NF-kappa B) and interferon regulatory factor 3 (IRF3). 1-[5-methoxy-2-(2-nitrovinyl)phenyl]pyrrolidine (MNP) has been previously synthesized in our laboratory. To evaluate the therapeutic potential of MNP, its effect on signal transduction via the TLR signaling pathways was examined. MNP was shown to inhibit the activation of NF-kappa B and IRF3 induced by TLR agonists, as well as to inhibit the expression of cyclooxygenase-2, inducible nitric oxide synthase, and interferon inducible protein-10. MNP also inhibited the activation of NF-kappa B and IRF3 induced by the overexpression of downstream signaling components of the MyD88 or TRIF-dependent signaling pathways. These results suggest that MNP can modulate MyD88- and TRIF-dependent signaling pathways of TLRs, leading to decreased inflammatory gene expression. (C) 2016 Elsevier B.V. All rights reserved.
引用
收藏
页码:193 / 200
页数:8
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