Inhibitory action of novel aromatic diamine compound on lipopolysaccharide-induced nuclear translocation of NF-kappaB without affecting IkappaB degradation.
4-Methyl-N1-(3-phenyl-propyl)-benzene-1,2-diamine (JSH-23) is a novel chemically synthetic compound. The aromatic diamine JSH-23 compound exhibited inhibitory effect with an IC(50) value of 7.1 microM on nuclear factor (NF)-kappaB transcriptional activity in lipopolysaccharide (LPS)-stimulated macrophages RAW 264.7, and interfered LPS-induced nuclear translocation of NF-kappaB without affecting IkappaB degradation. This mechanism of action is very rare for controlling NF-kappaB activation. Furthermore, the compound inhibited not only LPS-induced expressions of tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6 and inducible nitric oxide synthase and cyclooxygenase-2 but also LPS-induced apoptosis of the RAW 264.7 cells.
College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Cheongju 361-763, Republic of Korea.
Hyun-Mo
HM
Shin
Min-Hee
MH
Kim
Byung Hak
BH
Kim
Sang-Hun
SH
Jung
Yeong Shik
YS
Kim
Hye Ji
HJ
Park
Jin Tae
JT
Hong
Kyung Rak
KR
Min
Youngsoo
Y
Kim
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000235:genetics; D004926:Escherichia coli; D005786:Gene Expression Regulation / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism*; D007249:Inflammation; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D021381:Protein Transport / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D000072000:NF-KappaB Inhibitor alpha; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse