Suppression of TRIF-dependent signaling pathway of toll-like receptors by (E)-1-(2-(2-nitrovinyl)phenyl)pyrrolidine.
Eur J Pharmacol
; 721(1-3): 109-15, 2013 Dec 05.
Article
em En
| MEDLINE
| ID: mdl-24080550
ABSTRACT
Toll-like receptors (TLRs) play an important role in the recognition of microbial pathogens and induce innate immune responses. The recognition of microbial components by TLRs triggers the activation of myeloid differential factor 88 (MyD88)- and toll-interleukin-1 receptor domain-containing adapter inducing interferon-ß (TRIF)-dependent downstream signaling pathways. Previously, we synthesized (E)-1-(2-(2-nitrovinyl)phenyl)pyrrolidine (NVPP), which contains a nitrovinyl-phenyl and pyrrolidine. To evaluate the therapeutic potential of NVPP, its effect on signal transduction via the TRIF-dependent pathway of TLRs induced by lipopolysaccharide (LPS) or polyinosinic-polycytidylic acid (poly[IC]) was examined. NVPP inhibited LPS or poly[IC]-induced activation of nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3), and the phosphorylation of IRF3, as well as inhibiting the activation of interferon-inducible genes such as interferon inducible protein-10 (IP-10). These results suggest that NVPP can modulate TRIF-dependent signaling pathways of TLRs, potentially resulting in effective therapeutics for chronic inflammatory diseases.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirrolidinas
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Estirenos
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Transdução de Sinais
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Proteínas Adaptadoras de Transporte Vesicular
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Receptores Toll-Like
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Anti-Inflamatórios
Limite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
Ano de publicação:
2013
Tipo de documento:
Article