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Published on: December 29, 2012
Domon L, an immunopotentiating agent, acts as an NF-kappaB activator
S Tanaka1, H Sakurai, M Sugiura
1Lead Generation Research Laboratory, Tanabe Seiyaku Co., Ltd., Osaka, Japan.
Insights
Domon L, derived from Achromobacter stenohalis, boosts the immune system by enhancing nitric oxide (NO) production and activating NF-kappaB. This immunopotentiating effect suggests its potential as an anti-infectious agent in veterinary medicine.
Area of Science:
- Immunology
- Microbiology
- Molecular Biology
Background:
- Domon L is a heat-treated component of Achromobacter stenohalis.
- It is utilized for treating infectious diseases in animals.
Purpose of the Study:
- To investigate the immunopotentiating potential of Domon L.
- To elucidate the molecular mechanisms underlying Domon L's effects.
Main Methods:
- In vitro studies using murine macrophage RAW264.7 cells.
- Assessing nitric oxide (NO) formation and interferon-gamma (IFN-γ) synergy.
- Investigating Nuclear Factor-kappaB (NF-κB) activation via nuclear translocation and reporter gene assays.
- In vivo studies in rats measuring serum IL-6 and mucoprotein levels.
- Ex vivo analysis of spleen cell NO production.
Main Results:
- Domon L enhanced NO formation in RAW264.7 cells, particularly with IFN-γ.
- Domon L induced NF-κB nuclear translocation and activated NF-κB-dependent gene expression.
- In vivo, Domon L increased serum IL-6 and mucoprotein levels.
- Spleen cells from Domon L-treated rats showed significantly higher NO production upon stimulation.
Conclusions:
- Domon L exhibits immunopotentiating properties.
- The mechanism involves the activation of the NF-κB signaling pathway.
- Domon L demonstrates potential as an anti-infectious agent through immune modulation.
Abstract:
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.
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