Enhanced resistance to Salmonella enterica serovar Typhimurium infection in mice after coumarin treatment.
Coumarin and its derivatives are naturally occurring substances with multiple biological activities. Here we demonstrate that prophylactic peroral administration of coumarin or 7-hydroxycoumarin (7-OHC) enhances resistance to subsequent lethal Salmonella enterica Serovar Typhimurium infection in mice. 7-OHC decreased bacterial load in liver and spleen, and enhanced phagocytosis and bacterial killing by macrophages when applied in vitro and in vivo. 7-OHC treatment induced significant NO release in peritoneal macrophage cultures. The observed protective effect correlated with the induction of Th1-associated cytokines, such as IL-12, IFN-gamma, and TNF-alpha. These data demonstrate a clear immunomodulatory potential of coumarins which might have important therapeutic implications to enhance resistance to infection.
Stefanova
Tsvetanka
T
Department of Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, 26 Acad. G. Bonchev St., Sofia 1113, Bulgaria.
Nikolova
Nadja
N
Michailova
Anastasija
A
Mitov
Ivan
I
Iancov
Ianco
I
Zlabinger
Gerhard J
GJ
Neychev
Hristo
H
D000818:Animals; D003374:Coumarins / Q000097:blood / Q000276:immunology / Q000494:pharmacology*; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D026361:Reactive Nitrogen Species / Q000378:metabolism; D012485:Salmonella typhi / Q000276:immunology / Q000302:isolation & purification*; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014435:Typhoid Fever / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D014468:Umbelliferones / Q000097:blood / Q000276:immunology / Q000494:pharmacology*
D003374:Coumarins; D026361:Reactive Nitrogen Species; D014409:Tumor Necrosis Factor-alpha; D014468:Umbelliferones; D018664:Interleukin-12; C031477:7-hydroxycoumarin; D007371:Interferon-gamma; C030123:coumarin