Inhibitory effect of 6-hydroxy-7-methoxychroman-2-carboxylic acid phenylamide on nitric oxide and interleukin-6 production in macrophages

• Published in: Life sciences (1973) 2005-11, Vol.77 (25), p.3242-3257
• Main Authors: Rak Min, Kyung, Lee, Heesoon, Hak Kim, Byung, Chung, EunYong, Min Cho, Sung, Kim, Youngsoo
• Format: Article
• Language: English
• Subjects: Activator protein-1; Animals; Cell Line; Cell Survival - drug effects; Chromans - pharmacology; Down-Regulation; Interleukin-6; Interleukin-6 - biosynthesis; Lipopolysaccharides - pharmacology; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - enzymology; Macrophages, Peritoneal - metabolism; Male; Mice; Mice, Inbred ICR; NF-kappa B - metabolism; Nitric oxide; Nitric Oxide - biosynthesis; Nitric Oxide Synthase - biosynthesis; Nitric Oxide Synthase Type II; Nuclear factor-κB; Transcription Factor AP-1 - metabolism; Vitamin E analog
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2005.05.046

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-κB (NF-κB) and activator protein-1 (AP-1) has been documented. Finally, CP compound could provide an invaluable tool to investigate LPS-induced NF-κB and AP-1 activation, in addition to its therapeutic potential in NO- and IL-6-associated inflammatory diseases.