Domon L, an immunopotentiating agent, acts as an NF-kappaB activator.
Domon L, a heat-treated component of gram-negative bacterium Achromobacter stenohalis, is used for the treatment of infectious diseases of animals. Here, we investigated the immunopotentiating potential of Domon L. In vitro studies showed that Domon L enhanced nitric oxide (NO) formation from murine macrophage RAW264.7 cells in concert with interferon (IFN)-gamma. The effect of Domon L on NF-kappaB activation was investigated, in order to understand the molecular mechanisms of enhanced NO formation by Domon L. Domon L induced translocation of NF-kappaB to the nucleus in RAW264.7 cells. Induction of NF-kappaB dependent gene expression by Domon L was further confirmed using a transfectant containing an NF-kappaB-luciferase reporter gene. In vivo injection of Domon L elevated both serum IL-6 and mucoprotein, whose gene expression is partly under the control of NF-kappaB. The spleen cells of rats treated with Domon L produced much more NO when stimulated with LPS + IFN gamma than spleen cells of untreated rats. These results suggest that Domon L acts as an anti-infectious agent via NF-kappaB activation.
Tanaka
S
S
Lead Generation Research Laboratory, Tanabe Seiyaku Co., Ltd., Osaka, Japan.
Sakurai
H
H
Sugiura
M
M
Kawashima
K
K
Sugita
T
T
D042402:Achromobacter; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000421:Alcaligenes; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D051379:Mice; D016328:NF-kappa B / Q000096:biosynthesis* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D009573:Nitrites / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014162:Transfection
D000276:Adjuvants, Immunologic; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009573:Nitrites; D009838:Oligodeoxyribonucleotides; D011993:Recombinant Fusion Proteins; D009569:Nitric Oxide; D007371:Interferon-gamma