title: Leishmania (L.) amazonensis-induced inhibition of nitric oxide synthesis in host macrophages.
abstract: Inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production was demonstrated in J774-G8 macrophages infected with Leishmania (L.) amazonensis promastigotes. The downmodulation of NO production observed in infected and LPS-stimulated J774-G8 cells correlated with a reduction in inducible nitric oxide synthase (iNOS) activity. Reduction in iNOS activity was not paralleled by decreased iNOS mRNA expression, suggesting that the parasite affects post-transcriptional events of NO synthesis. Supplementation with L-arginine or tetrahydrobiopterin did not increase NO production, suggesting that inhibition is not due to an insufficiency of substrate or co-factor. Treatment with anti-IL-10, anti-IL-4 or anti-TGF-beta neutralizing antibodies also failed to increase NO production, indicating that these cytokines are not involved in the observed parasite-induced inhibition of NO synthesis. However, treatment of the cultures with IFN-gamma resulted in a marked increase in NO production by infected LPS-stimulated cells. These results show that although L.(L.) amazonensis infection inhibits iNOS activity and NO production by J774-G8 cells, activation by IFN-gamma is capable of overriding the suppression of NO synthesis.
authors.affiliation: Departamento de Fisiologia e Patologia/Laboratório de Tecnologia Farmacêutica, UFPB, João Pessoa, CEP 58051-970, PB, Brazil.
authors.forename: Filomena M Perrella
authors.initials: FM
authors.lastname: Balestieri
authors.forename: Allan R Pires
authors.initials: AR
authors.lastname: Queiroz
authors.forename: Cristoforo
authors.initials: C
authors.lastname: Scavone
authors.forename: Vlaudia M Assis
authors.initials: VM
authors.lastname: Costa
authors.forename: Manoel
authors.initials: M
authors.lastname: Barral-Netto
authors.forename: Ises de Almeida
authors.initials: Ide A
authors.lastname: Abrahamsohn
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D007891:Leishmania / Q000472:pathogenicity*; D007896:Leishmaniasis / Q000469:parasitology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse