Suppressive effect of novel aromatic diamine compound on nuclear factor-κB-dependent expression of inducible nitric oxide synthase in macrophages

N-1-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)-kappa B activation has been documented. BNID compound exhibited dose-dependent inhibitory effect on LPS-mediated NF-kappa B transcriptional activity in the macrophages. Further, the compound inhibited LPS-mediated nuclear translocation of NF-kappa B p65 and DNA binding activity of NF-kappa B complex, in parallel, but did not affect LPS-mediated degradation of inhibitory kappa B alpha protein (I kappa B alpha). These results indicate that BMD compound could inhibit nuclear localization step of NF-kappa B p65 without affecting I kappa B alpha gradation. Finally, BMD compound could provide an invaluable tool to investigate NF-kappa B-dependent iNOS expression, in addition to its therapeutic potential in NO-associated inflarnmatory diseases. (c) 2005 Elsevier B.V. All rights reserved.