Prostaglandin E2 down-regulates viable Bacille Calmette-Guérin-induced macrophage cytotoxicity against murine bladder cancer cell MBT-2 in vitro.
The regulatory effect of prostaglandin (PG) E2 and a cyclooxygenase (COX) inhibitor on Bacille Calmette-Guérin (BCG)-induced macrophage cytotoxicity in a bladder cancer cell, MBT-2, was studied in vitro. BCG stimulated thioglycollate-elicited murine peritoneal exudate cells (PEC) to induce cytotoxic activity and to produce cytokines such as interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha and PGE2. NS398, a specific COX-2 inhibitor, and indomethacin (IM), a COX-1 and COX-2 inhibitor, enhanced viable BCG-induced cytotoxic activity and IFN-gamma and TNF-alpha production of PEC. However, NS398 and IM did not enhance these activities induced by killed BCG. Enhanced cytotoxicity was mediated by increased amounts of IFN-gamma and TNF-alpha. Exogenous PGE2 reduced cytotoxic activity and IFN-gamma and TNF-alpha production of PEC. These results suggest that PGE2 produced by BCG-activated macrophages has a negative regulatory effect on the cytotoxic activity of macrophages. Accordingly, a PG synthesis inhibitor may be a useful agent to enhance BCG-induced antitumour activity of macrophages.
Yamada
H
H
Department of Urology and Immunology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan. yama-uki@med.uoeh-u.ac.jp
Kuroda
E
E
Matsumoto
S
S
Matsumoto
T
T
Yamada
T
T
Yamashita
U
U
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001500:BCG Vaccine / Q000276:immunology*; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D015232:Dinoprostone / Q000494:pharmacology*; D015536:Down-Regulation; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D009578:Nitrobenzenes / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology; D001749:Urinary Bladder Neoplasms / Q000276:immunology*
D000906:Antibodies; D001500:BCG Vaccine; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D009578:Nitrobenzenes; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D007371:Interferon-gamma; D015232:Dinoprostone; D007213:Indomethacin