Inhibitory effect of 6-hydroxy-7-methoxychroman-2-carboxylic acid phenylamide on nitric oxide and interleukin-6 production in macrophages.
6-Hydroxy-7-methoxychroman-2-carboxylic acid phenylamide (CP compound) is a novel chemically synthetic compound with vitamin E-like chemical structure. In the present study, the CP compound was discovered to inhibit nitric oxide (NO) and interleukin (IL)-6 productions in lipopolysaccharide (LPS)-stimulated macrophages. Further, CP compound attenuated LPS-induced synthesis of mRNA and protein levels of inducible NO synthase (iNOS), in parallel, and inhibited iNOS promoter activity. In the similar way, CP compound inhibited LPS-induced synthesis of IL-6 transcript but also IL-6 promoter activity. These results indicate that CP compound could down-regulate LPS-induced iNOS and IL-6 expression at the transcription step. As a mechanism of the anti-inflammatory action shown by CP compound, suppression of LPS-induced activation of both nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) has been documented. Finally, CP compound could provide an invaluable tool to investigate LPS-induced NF-kappaB and AP-1 activation, in addition to its therapeutic potential in NO- and IL-6-associated inflammatory diseases.
College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Cheongju 361-763, Korea. krmin@chungbuk.ac.kr
Kyung
K
Rak Min
Heesoon
H
Lee
Byung
B
Hak Kim
Eunyong
E
Chung
Sung
S
Min Cho
Youngsoo
Y
Kim
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D015536:Down-Regulation; D015850:Interleukin-6 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D018808:Transcription Factor AP-1 / Q000378:metabolism
C495393:6-hydroxy-7-methoxychroman-2-carboxylic acid phenylamide; D002839:Chromans; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse