title: IL-4 and IL-10 inhibition of IFN-gamma- and TNF-alpha-dependent nitric oxide production from bovine mononuclear phagocytes exposed to Babesia bovis merozoites.
abstract: The requirement for IFN-gamma and/or TNF-alpha as co-stimulants with Babesia bovis merozoites for nitric oxide (NO) production was examined, as well as the regulatory role of IL-4 and IL-10. Purified B. bovis merozoites did not induce the production of NO in undifferentiated monocytes without addition of exogenous IFN-gamma and TNF-alpha unless the monocytes taken ex vivo were producing TNF-alpha endogenously. Under the latter condition, the NO production resulting from merozoite stimulation remained IFN-gamma-dependent. There was no evidence for endogenous synthesis of TNF-alpha in monocyte-derived macrophages (MDM), and merozoites alone were incapable of inducing TNF-alpha mRNA in MDM. However, while merozoites plus IFN-gamma induced TNF-alpha mRNA expression in MDM, NO was not produced. Both IL-4 and IL-10 inhibited expression of iNOS and production of NO in merozoite-stimulated monocytes.
authors.affiliation: Animal Disease Research Unit, USDA-ARS, Washington State University, 3003 ADBF, P.O. Box 646630, Pullman, WA 99164-6630, USA. wgoff@vetmed.wsu.edu
authors.forename: W L
authors.initials: WL
authors.lastname: Goff
authors.forename: W C
authors.initials: WC
authors.lastname: Johnson
authors.forename: S M
authors.initials: SM
authors.lastname: Parish
authors.forename: G M
authors.initials: GM
authors.lastname: Barrington
authors.forename: T H
authors.initials: TH
authors.lastname: Elsasser
authors.forename: W C
authors.initials: WC
authors.lastname: Davis
authors.forename: R A
authors.initials: RA
authors.lastname: Valdez
mesh_terms: D000818:Animals; D016793:Babesia bovis / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D002417:Cattle; D002454:Cell Differentiation; D015870:Gene Expression / Q000187:drug effects; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010586:Phagocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II