title: The role of nitric oxide in parasitic diseases.
abstract: Murine macrophages express high levels of nitric oxide synthase and produce large amounts of nitric oxide (NO) when stimulated with certain cytokines in the presence of a trace amount of lipopolysaccharide (LPS). The stimulatory cytokines include interleukin-1 (IL-1), interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and migration inhibitory factor. Activated macrophages are highly effective killers of intra- and extra-cellular pathogens. However, as excessive NO can lead to immunopathology (diabetes, graft-v.-host disease, EAE, liver cirrhosis, rheumatoid arthritis), NO production is necessarily under tight regulation. A number of cytokines, including IL-4, IL-10 and transforming growth factor-beta, can down regulate the induction of NO synthase in macrophages. In addition, macrophages exposed to LPS alone and then stimulated with a mix of IFN-gamma and LPS express significantly lower levels of NO synthase than cells stimulated without pre-exposure to LPS. Furthermore, NO can reduce the activity of NO synthase by feedback inhibition, and also inhibit the production of IFN-gamma by Th1 cells (thus turning off its own synthesis from upstream). The regulatory pathways involve tyrosine kinase and protein kinase C.
authors.affiliation: Department of Immunology, University of Glasgow, U.K.
authors.forename: F Y
authors.initials: FY
authors.lastname: Liew
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D004790:Enzyme Induction; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase; D010272:Parasitic Diseases / Q000378:metabolism*; D051381:Rats
chemical_list: D016207:Cytokines; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases