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

• Published in: European journal of pharmacology Vol. 521; no. 1; pp. 1 - 8
• Main Authors: Shin, Hyun-Mo, Byung Hak Kim, Eun Yong Chung, Jung, Sang-Hun, Yeong Shik Kim, Kyung Rak Min, Kim, Youngsoo
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 03.10.2005; Elsevier
• Subjects: Anti-inflammation; Aromatic diamine compound; Biological and medical sciences; Inducible nitric oxide synthase; Macrophages; Medical sciences; Nuclear factor-κB; Pharmacology. Drug treatments; Nuclear factor-κB; Macrophages; Aromatic diamine compound; Inducible nitric oxide synthase; Anti-inflammation; Enzyme; Nuclear factor-κ-B; Aromatic compound; Inflammation; Oxidoreductases; Transcription factor NFκB; Nitric-oxide synthase; Macrophage
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2005.07.013

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)-κB activation has been documented. BMD compound exhibited dose-dependent inhibitory effect on LPS-mediated NF-κB transcriptional activity in the macrophages. Further, the compound inhibited LPS-mediated nuclear translocation of NF-κB p65 and DNA binding activity of NF-κB complex, in parallel, but did not affect LPS-mediated degradation of inhibitory κBα protein (IκBα). These results indicate that BMD compound could inhibit nuclear localization step of NF-κB p65 without affecting IκBα degradation. Finally, BMD compound could provide an invaluable tool to investigate NF-κB-dependent iNOS expression, in addition to its therapeutic potential in NO-associated inflammatory diseases.