Immunosuppressive activities of 6(5H)-phenanthridinone, a new poly(ADP-ribose)polymerase inhibitor.
6(5H)-phenanthridinone, a recently identified poly(ADP-ribose)polymerase (PARP) inhibitor, is able, at micromolar concentrations, to inhibit concanavalin A-induced lymphocyte proliferation and to potentiate the effect of gamma radiation upon murine spleen cells. When added at the onset of a mixed lymphocyte culture, this compound strongly depresses the induction of primary allogeneic (anti-H2k) cytotoxic T-lymphocytes (CTLs). Lymphokine-activated killer (LAK) induction was also found to be impaired by the PARP inhibitor. Taken together, these results clearly indicate that PARP plays a key-role in immune reactions involving cytotoxicity and that 6(5H)-phenanthridinone could be considered as a potent immunomodulator.
Weltin
D
D
Institut d'Hématologie et d'Immunologie, Strasbourg, France.
Picard
V
V
Aupeix
K
K
Varin
M
M
Oth
D
D
Marchal
J
J
Dufour
P
P
Bischoff
P
P
D000166:Acridines / Q000494:pharmacology; D054831:Acridones; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D005720:Gamma Rays; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000528:radiation effects; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D010616:Phenanthrenes / Q000494:pharmacology*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology
D000166:Acridines; D054831:Acridones; D001549:Benzamides; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D007546:Isoquinolines; D010616:Phenanthrenes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011994:Recombinant Proteins; D003208:Concanavalin A; C095653:1,5-dihydroxyisoquinoline; C041300:acridone; C025160:3-aminobenzamide; C040601:phenanthridone; C025159:3-methoxybenzamide