title: Enhanced resistance to Salmonella enterica serovar Typhimurium infection in mice after coumarin treatment.
abstract: 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.
authors.affiliation: Department of Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, 26 Acad. G. Bonchev St., Sofia 1113, Bulgaria.
authors.forename: Tsvetanka
authors.initials: T
authors.lastname: Stefanova
authors.forename: Nadja
authors.initials: N
authors.lastname: Nikolova
authors.forename: Anastasija
authors.initials: A
authors.lastname: Michailova
authors.forename: Ivan
authors.initials: I
authors.lastname: Mitov
authors.forename: Ianco
authors.initials: I
authors.lastname: Iancov
authors.forename: Gerhard J
authors.initials: GJ
authors.lastname: Zlabinger
authors.forename: Hristo
authors.initials: H
authors.lastname: Neychev
mesh_terms: 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*
chemical_list: D003374:Coumarins; D026361:Reactive Nitrogen Species; D014409:Tumor Necrosis Factor-alpha; D014468:Umbelliferones; D018664:Interleukin-12; C031477:7-hydroxycoumarin; D007371:Interferon-gamma; C030123:coumarin