Format

Send to

Choose Destination
See comment in PubMed Commons below
Biochem Pharmacol. 1997 Mar 21;53(6):773-82.

Cytotoxicity to macrophages of tetrandrine, an antisilicosis alkaloid, accompanied by an overproduction of prostaglandins.

Author information

  • 1Pharmacology Group, King's College London, U.K.

Erratum in

  • Biochem Pharmacol 1997 Jun 15;53(12):1946.

Abstract

Tetrandrine, an anti-inflammatory immunosuppressive bisbenzylisoquinoline alkaloid of Chinese herbal origin, is widely used to treat silicosis and interferes with the regulation of calcium in many cell types. We investigated its effect on the cellular integrity of macrophages and on their ability to generate prostaglandins and nitric oxide, mediators of inflammation with immunomodulatory roles. Tetrandrine at 10(-7) M to 10(-4) M caused dose- and time-dependent loss of cell viability of mouse peritoneal macrophages, guinea-pig alveolar macrophages and mouse macrophage-like J774 cells. Loss of viability (50%) occurred within 1-3 hr and required approximately 5 x 10(-6) M tetrandrine. Loss of macrophage viability after tetrandrine treatment was accompanied by the generation of large amounts of prostaglandin E2 (PGE2), to levels 285-877% of control. Coincubation with indomethacin abolished PGE2 generation, but did not prevent cell death. Tetrandrine did not cause generation of nitric oxide. Verapamil also reduced the viability of mouse peritoneal macrophages and J774 cells, but did not cause PGE2 overproduction, except at 10(-4) M in mouse peritoneal macrophages. In macrophages cultured with lipopolysaccharide and interferon-gamma to induce the generation of large amounts of both PGE2 and nitric oxide, tetrandrine reduced mediator release and their forming enzymes (cyclo-oxygenase-2 and inducible nitric oxide synthase), secondary to cytotoxicity. The predominant action of tetrandrine is to exert a cytotoxic effect on macrophages, perhaps by interfering with calcium homeostasis; this leads to overproduction of immunomodulatory but proinflammatory prostaglandin. This may be relevant to its protective actions in human fibrosing silicosis, in which there is alveolar macrophage involvement.

PMID:
9113098
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk