Inhibitory mechanism of chroman compound on LPS-induced nitric oxide production and nuclear factor-kappaB activation.
6-Hydroxy-7-methoxychroman-2-carboxylic acid phenylamide (KL-1156) is a novel chemically synthetic compound. In the present study, the chroman KL-1156 compound was found to inhibit lipopolysaccharide (LPS)-induced nitric oxide production in macrophages RAW 264.7. KL-1156 compound attenuated LPS-induced synthesis of both mRNA and protein of inducible nitric oxide synthase (iNOS), in parallel, and inhibited LPS-induced iNOS promoter activity, indicating that the chroman compound down-regulated iNOS expression at transcription level. As a mechanism of the anti-inflammatory action shown by KL-1156 compound, suppression of nuclear factor (NF)-kappaB has been documented. KL-1156 compound exhibited a dose-dependent inhibitory effect on LPS-induced NF-kappaB transcriptional activity in macrophages RAW 264.7. Furthermore, the compound inhibited LPS-induced nuclear translocation of NF-kappaB p65 and DNA binding activity of NF-kappaB complex, in parallel, but did not affect IkappaBalpha degradation. Taken together, this study demonstrated that chroman KL-1156 compound interfered with nuclear translocation step of NF-kappaB p65, which was attributable to its anti-inflammatory action.
Kim
Byung Hak
BH
College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Cheongju 361-763, Republic of Korea.
Reddy
Alavala Matta
AM
Lee
Kum-Ho
KH
Chung
Eun Yong
EY
Cho
Sung Min
SM
Lee
Heesoon
H
Min
Kyung Rak
KR
Kim
Youngsoo
Y
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D002460:Cell Line; D002839:Chromans / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D020672:I-kappa B Proteins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D015394:Molecular Structure; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011401:Promoter Regions, Genetic; D051996:Transcription Factor RelA; D014158:Transcription, Genetic
C495393:6-hydroxy-7-methoxychroman-2-carboxylic acid phenylamide; D002839:Chromans; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D004247:DNA; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse