RESUMEN

Toll-like receptor 4 (TLR4) is known to play an important role in innate immune responses. In the present study, chemically synthetic compound of N(1)-benzyl-4-methylbenzene-1,2-diamine (BMD) was discovered to inhibit nitric oxide (NO) production in macrophages RAW 264.7 stimulated with lipopolysaccharide (LPS) or fibronectin as TLR4 activators. The BMD compound attenuated LPS-induced synthesis of both mRNA and protein of NO synthase (iNOS), and inhibited LPS or fibronectin-mediated iNOS promoter activity, indicating that the compound down-regulated iNOS expression at transcription level. As a mode of the anti-inflammatory action shown by BMD compound, inhibitory effect on nuclear factor (NF)-kappaB activation was also investigated in macrophages RAW 264.7 stimulated with the TLR4 activators.

Asunto(s)

Antiinflamatorios no Esteroideos/farmacología , Benceno/farmacología , Diaminas/farmacología , Receptor Toll-Like 4/biosíntesis , Animales , Antiinflamatorios no Esteroideos/química , Benceno/química , Línea Celular , Diaminas/química , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Regulación Enzimológica de la Expresión Génica , Ratones , Receptor Toll-Like 4/antagonistas & inhibidores