Suppressive effects of E3330, a novel quinone derivative, on tumor necrosis factor-alpha generation from monocytes and macrophages

• Published in: Agents and actions Vol. 37; no. 3-4; p. 297
• Main Authors: Miyamoto, K, Nagakawa, J, Hishinuma, I, Hirota, K, Yasuda, M, Yamanaka, T, Katayama, K, Yamatsu, I
• Format: Journal Article
• Language: English
• Published: Switzerland 01.11.1992
• Subjects: Animals; Base Sequence; Benzoquinones - pharmacology; Blotting, Northern; Cells, Cultured; Depression, Chemical; Humans; Kupffer Cells - drug effects; Kupffer Cells - metabolism; Lipopolysaccharides - pharmacology; Macrophages - drug effects; Macrophages - metabolism; Male; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Monocytes - drug effects; Monocytes - metabolism; Propionates - pharmacology; Propionibacterium acnes - immunology; Rats; Rats, Inbred F344; RNA - isolation & purification; RNA - metabolism; Spleen - cytology; Spleen - drug effects; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 0065-4299
• DOI: 10.1007/BF02028123

E3330 [(2E)-3-[5-(2,3-dimethoxy-6-methyl-1,4-benzoquinoyl)]-2-nonyl-2- propenoic acid], a novel synthesized hepatoprotective compound, has suppressive effects on tumor necrosis factor-alpha (TNF-alpha) generation from monocytes/macrophages in vitro. E3330 (1-100 microM) reduced lipopolysaccharide (LPS, 10 mg/ml or 1 microgram/ml)-induced TNF-alpha generation from rat resident and Propionibacterium acnes (P. acnes)-elicited peritoneal macrophages, rat and human monocytes, rat Kupffer cells, and splenic mononuclear cells in a concentration-dependent manner. E3330 also (1-100 microM) suppressed TNF-alpha generation stimulated with egg-albumin immune complex in rat P. acnes-elicited peritoneal macrophages. Northern blot analysis showed that LPS-induced expression of TNF-alpha messenger RNA (mRNA) in human blood monocytes was suppressed by E3330. These findings indicate that E3330 has a suppressive effect on TNF-alpha generation from monocytes/macrophages, regardless of origin or species, and this effect is based in part on the suppression of TNF-alpha mRNA expression.