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

  • Molecular Immunopathology
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Abstract

E3330 {(2E)-3-[5-(2,3-dimethoxy-6-methyl-1,4-benzoquinoyl)]-2-nonly-2-propenoic acid}, a novel synthesized hepatoprotective compound, has suppressive effects on tumor necrosis factor-α (TNF-α) generation from monocytes/macrophagesin vitro. E3330 (1–100 μM) reduced lipopolysaccharide (LPS, 10 mg/ml or 1μg/ml)-induced TNF-α generation from rat resident andPropionibacterium 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 μM) suppressed TNF-α generation stimulated with egg-albumin immune complex in ratP. acnes-elicited peritoneal macrophages. Northern blot analysis showed that LPS-induced expression of TNF-α messenger RNA (mRNA) in human blood monocytes was suppressed by E3330. These findings indicate that E3330 has a suppressive effect on TNF-α generation from monocytes/macrophages, regardless of origin or species, and this effect is based in part on the suppression of TNF-α mRNA expression.

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References

  1. Y. Muto, K. T. Nouri-Aria, A. Meager, G. J. M. Alexander, A. L. W. F. Eddleston and R. Williams,Enhanced tumor necrosis factor and interleukin-1 in fulminant hepatic failure. Lancetii, 72–74 (1988).

    Google Scholar 

  2. C. J. McClain and D. A. Cohen,Increased tumor necrosis factor production by monocytes in alcoholic hepatitis. Hepatology9, 349–651 (1989).

    PubMed  Google Scholar 

  3. K. Yoshioka, S. Kakumu, M. Arao, Y. Tsutsumi and M. Inoue,Tumor necrosis factor-α production by peripheral blood mononuclear cells of patients with chronic liver disease. Hepatology10, 769–773 (1989).

    PubMed  Google Scholar 

  4. G. Tiegs, M. Wolter and A. Wendel,Tumor necrosis factor is a terminal mediator in galactosamine/endotoxin-induced hepatitis in mice. Biochem. Pharmacol.38, 627–631 (1989).

    PubMed  Google Scholar 

  5. I. Hishinuma, J.Nagakawa, K. Hirota, K. Miyamoto, T. Yamanaka and K. Katayama,Involvement of tumor necrosis factor-α in development of hepatic injury in galactosamine-sensitized mice. Hepatology12, 1187–1191 (1990).

    PubMed  Google Scholar 

  6. J. Nagakawa, I. Hishinuma, K. Hirota, K. Miyamoto, T. Yamanaka, K. Tsukidate, K. Katayama and I. Yamatsu,Involvement of tumor necrosis factor-α in the pathogenesis of activated macrophage-mediated hepatitis. Gastroenterology99, 758–765 (1990).

    PubMed  Google Scholar 

  7. J. Nagakawa, I. Hishinuma, K. Miyamoto, K. Hirota, M. Yasuda, T. Yamanaka, K. Katayama and I. Yamatsu,Protective effects of (2E)-3-[5-(2,3-dimethoxy-6-methyl-1,4-benzoquinoyl)]-2-nonyl-2-propenoic acid on endotoxininduced hepatitis in mice. J. Phamaco. Exp. Therapeutic. (in press).

  8. D. Gemsa, W. Kramer, I. Napierski, E. Bärlin, G. Till and K. Resch,Potentiation of macrophage tumor cytostasis by tumor-induced ascites. J. Immunol.126, 2143 (1981).

    PubMed  Google Scholar 

  9. J. R. Koski, D. G. Poplack and R. M. Blaese,A nonspecific esterase stain for the identification of monocytes and macrophages. Inin vitro Methods in Cell-Mediated and Tumor Immunity. (Eds. B. R. Bloom and J. R. David) p. 359 Academic Press, New York 1976.

    Google Scholar 

  10. A. Boyum,Isolation of mononuclear cells and granulocytes from human blood. Scand. J. Clin. Invest. Suppl.21, 77–89 (1984).

    Google Scholar 

  11. D. L. Knook and E. C. H. Sleyster,Separation of Kupffer and endothelial cells of rat liver by centrifugal elutriation. Exp. Cell Res.139, 444–449 (1982).

    Google Scholar 

  12. Y. Kobayashi, M. Asada, M. Higuchi and T. Osawa,Human T cell hybridomas producing lymphokines: I. Establishment and characterization of human T cell hybridomas producing lymphotoxin and migration inhibitory factor. J. Immunol.128, 2714–2718 (1982).

    PubMed  Google Scholar 

  13. B. B. Aggarwal, W. J. Kohr, P. E. Hass, B. Moffat, S. A. Spencer, W. J. Henzel, T. S. Bringman, G. E. Nedwin, D. V. Goeddel and R. N. Harkins,Tumor necrosis factor: Production, purification, and characterization. J. Biol. Chem.260, 2345–2354 (1985).

    PubMed  Google Scholar 

  14. S. Yamazaki, E. Onishi, K. Enami, K. Natori, M. Kohase, H. Sakamoto, M. Tanouchi and H. Hayashi,Proposal of standard methods and reference for assaying recombinant human necrosis factor. Japan J. Med. Sci. Biol.39, 105–118, (1986).

    Google Scholar 

  15. J. M. Chirgwin, A. E. Przybyla, R. J. MacDonal and W. J. Rutter,Isolation of biologically active RNA form sources enriched in ribonuclease. Biochemistry18, 5295 (1979).

    Google Scholar 

  16. V. Glisin, R. Crvenjqakav and C. Byus,Ribonucleic acid isolation by cesium chloride centrifugation. Biochemistry13, 2633 (1974).

    PubMed  Google Scholar 

  17. G. Vitri and J. A. Hamilton,Modulation of urokinase-type plasminogen activator messenger RNA levels in human synovial fibroblasts by interleukin-1, retinoic acid and a glucocorticoid. Arthritis Rheum.31, 1046–1051 (1988).

    PubMed  Google Scholar 

  18. R. J. Schwartz, J. A. Haron, K. N. Rothblum and A. Dugaiczyk,Regulation of muscle differentiation: cloning of sequences from β-actin messenger ribonucleic acid. Biochemistry19, 5883 (1980).

    PubMed  Google Scholar 

  19. T. Decker, M.-L. Lohman-Matthes and G. E. Gifford,Cellassociated tumor necrosis factor (TNF) as a killing mechanism of cytotoxic macrophages. J. Immunol.138, 957 (1987).

    PubMed  Google Scholar 

  20. H. C. Kelker, J. D. Oppenheim, D. Stoner-Wolff, D. Henriksen-DeStrefano, B. B. Aggarwal, H. C. Stevenson and J. Vilcek,Characterization of human tumor necrosis factor produced by peripheral blood monocytes and its separation from lymphotoxin. Int. J. Cancer36, 69 (1985).

    PubMed  Google Scholar 

  21. D. V. Goeddel, B. B. Aggarwal, P. W. Gray, D. W. Leung, G. E. Nedwin, M. A. Palladino, J. S. Paton, D. Pennica, H. M. Shepard, B. J. Sugarman and G. H. W. Wong,Tumor necrosis structure and biological activities. Cold spring Har. Symp. Quant. Biol.51, 597 (1986).

    Google Scholar 

  22. B. Beulter, N. Krochin, I. W. Milsark, C. Luedke and A. Cerami,Control of cachectin (tumor necrosis factor) synthesis: Mechanisms of endotoxin resistance. Science232, 977–990 (1986).

    PubMed  Google Scholar 

  23. S. L. Kunkel, M. Splengler, M. A. May, R. Splengler, J. Larrick and D. Remick,Prostaglandin E2 regulates macrophage-derived tumor necrosis factor gene expression. J. Biol. Chem.263, 5380–5384 (1988).

    PubMed  Google Scholar 

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Miyamoto, K., Nagakawa, J., Hishinuma, I. et al. Suppressive effects of E3330, a novel quinone derivative, on tumor necrosis factor-α generation from monocytes and macrophages. Agents and Actions 37, 297–304 (1992). https://doi.org/10.1007/BF02028123

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  • DOI: https://doi.org/10.1007/BF02028123

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