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Life Sci ; 77(25): 3242-57, 2005 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-15978634

RESUMO

6-Hydroxy-7-methoxychroman-2-carboxylic acid phenylamide (CP compound) is a novel chemically synthetic compound with vitamin E-like chemical structure. In the present study, the CP compound was discovered to inhibit nitric oxide (NO) and interleukin (IL)-6 productions in lipopolysaccharide (LPS)-stimulated macrophages. Further, CP compound attenuated LPS-induced synthesis of mRNA and protein levels of inducible NO synthase (iNOS), in parallel, and inhibited iNOS promoter activity. In the similar way, CP compound inhibited LPS-induced synthesis of IL-6 transcript but also IL-6 promoter activity. These results indicate that CP compound could down-regulate LPS-induced iNOS and IL-6 expression at the transcription step. As a mechanism of the anti-inflammatory action shown by CP compound, suppression of LPS-induced activation of both nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) has been documented. Finally, CP compound could provide an invaluable tool to investigate LPS-induced NF-kappaB and AP-1 activation, in addition to its therapeutic potential in NO- and IL-6-associated inflammatory diseases.


Assuntos
Cromanos/farmacologia , Interleucina-6/biossíntese , Macrófagos Peritoneais/efeitos dos fármacos , Óxido Nítrico/biossíntese , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo , Lipopolissacarídeos/farmacologia , Macrófagos Peritoneais/enzimologia , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Óxido Nítrico Sintase/biossíntese , Óxido Nítrico Sintase Tipo II , Fator de Transcrição AP-1/metabolismo
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