Suppressive effects of E3330, a novel quinone derivative, on tumor necrosis factor-alpha generation from monocytes and macrophages.
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.
Miyamoto
K
K
Tsukuba Research Laboratories, Eisai Co. Ltd., Ibaraki, Japan.
Nagakawa
J
J
Hishinuma
I
I
Hirota
K
K
Yasuda
M
M
Yamanaka
T
T
Katayama
K
K
Yamatsu
I
I
D000818:Animals; D001483:Base Sequence; D016227:Benzoquinones / Q000494:pharmacology*; D015152:Blotting, Northern; D002478:Cells, Cultured; D003864:Depression, Chemical; D006801:Humans; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology*; D011425:Propionibacterium acnes / Q000276:immunology; D012313:RNA / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D016227:Benzoquinones; D008070:Lipopolysaccharides; D011422:Propionates; D014409:Tumor Necrosis Factor-alpha; C075569:E 3330; D012313:RNA