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  • Title: Suppressive effect of novel aromatic diamine compound on nuclear factor-kappaB-dependent expression of inducible nitric oxide synthase in macrophages.
    Author: Shin HM, Byung Hak Kim, Eun Yong Chung, Jung SH, Yeong Shik Kim, Kyung Rak Min, Kim Y.
    Journal: Eur J Pharmacol; 2005 Oct 03; 521(1-3):1-8. PubMed ID: 16183054.
    Abstract:
    N1-benzyl-4-methylbenzene-1,2-diamine (BMD) is a novel synthetic compound. In the present study, BMD compound was discovered to inhibit nitric oxide (NO) production in macrophages RAW 264.7. BMD compound attenuated lipopolysaccharide (LPS)-induced synthesis of both mRNA and protein of inducible nitric oxide synthase (iNOS), and inhibited LPS-induced iNOS promoter activity, indicating that the aromatic diamine compound could down-regulate iNOS expression at the transcription level. As a mechanism of the anti-inflammatory action, suppression of BMD compound on nuclear factor (NF)-kappaB activation has been documented. BMD compound exhibited dose-dependent inhibitory effect on LPS-mediated NF-kappaB transcriptional activity in the macrophages. Further, the compound inhibited LPS-mediated nuclear translocation of NF-kappaB p65 and DNA binding activity of NF-kappaB complex, in parallel, but did not affect LPS-mediated degradation of inhibitory kappaBalpha protein (IkappaBalpha). These results indicate that BMD compound could inhibit nuclear localization step of NF-kappaB p65 without affecting IkappaBalpha degradation. Finally, BMD compound could provide an invaluable tool to investigate NF-kappaB-dependent iNOS expression, in addition to its therapeutic potential in NO-associated inflammatory diseases.
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