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The capacity of recombinant interferon-alpha, -beta and -gamma, of bacterial lipopolysaccharide and of recombinant tumour necrosis factor-alpha to induce indoleamine 2,3-dioxygenase and synthesis of pteridines was studied in human peripheral blood mononuclear cells, human macrophages and normal
Bacterial lipopolysaccharides (LPS) induce the activity of guanosine triphosphate (GTP)-cyclohydrolase I (GTP-CHI), the first enzyme in the biosynthesis of tetrahydrobiopterin (H4bip) from GTP in endothelial cells and macrophages. In these and other cells, LPS also acts costimulatory with cytokines,
Screening of a pteridine-based compound library led to the identification of compounds exhibiting immunosuppressive as well as anti-inflammatory activity. Optimization afforded a series of 2-amino-4-N-piperazinyl-6-(3,4-dimethoxyphenyl)pteridine analogues. The most potent congeners in this series
During cell-mediated immune response, increased amounts of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) are released. In the present study, we investigated the potential of these two cytokines to mediate apoptosis and to alter signal transduction pathways involved in
We investigated intracellular pteridine concentrations, activities of pteridine biosynthetic enzymes and formation of nitrogen oxides from arginine in human peripheral-blood-derived macrophages and in myelomonocytoma (THP-1) cells, as well as in murine peritoneal and spleen-derived macrophages and
A series of analogues of pentoxifylline metabolites were prepared in the purine, pteridine, [1,2,5]-thiadiazolo[3,4-d]pyrimidine, and quinazoline ring systems and evaluated for their ability to inhibit the production of tumor necrosis factor-alpha (TNF alpha) in human peripheral blood monocytes
Elevated production of tumor necrosis factor (TNF) plays a central role in the pathogenesis of many inflammatory diseases, such as rheumatoid arthritis and Crohn's disease. Naturally occurring pteridine analogs have been reported to have potent immunomodulatory activity, especially on TNF
Stimulation of nitric oxide (NO) synthase in endothelial cells by Ca2+ influx leads to increased intracellular levels of cGMP. NO synthase from various sources is known to use tetrahydrobiopterin, flavins, and NADPH as cofactors. We studied the effect of interferon-gamma, tumor necrosis
Obesity activates both innate and adaptive immune responses in adipose tissue. Elevated levels of eosinophils with depression of monocyte and neutrophil indicate the deficiencies in the immune system of morbidly obese individuals. Actually, adipose tissue macrophages are functional
The influence of UVB irradiation on the metabolic pathway for the production of L-tyrosine from L-phenylalanine in the human epidermis has been examined in 12 healthy volunteers with photo skin types I-VI (Fitzpatrick classification). This metabolic pathway involves the induction of
To get a measure of the extent of induction of nitric oxide synthase in infection with human immunodeficiency virus type-1 (HIV-1) in vivo, we estimated serum nitrite plus nitrate concentrations in 110 HIV-1 infected individuals compared to 76 blood donors. To monitor cytokine action and to measure
The pteridine neopterin is a marker of immunological activation and has been shown to be a useful marker of graft-versus-host disease (GVHD) in bone marrow transplant patients. High levels of both neopterin and interferon-gamma (IFN-gamma) were produced in vitro during mixed lymphocyte responses,
The neopterin derivatives, neopterin and 7,8-dihydroneopterin, modulate the cellular oxidant-antioxidant balance as well as the expression of the inducible nitric oxide synthase (iNOS) gene. Since apoptosis can be induced by reactive oxygen intermediates and nitric oxide (NO) we investigated whether
BACKGROUND
The nitric oxide synthase cofactor tetrahydrobiopterin (BH4) is involved in the regulation of endothelium-dependent vascular functions mediated by nitric oxide. Vascular endothelial cells synthesize and secrete large amounts of BH4 on cytokine activation. There is scant knowledge about
OBJECTIVE
Neopterin (NT) is a compound of low molecule-based pteridine. It is secreted by macrophages as a response to the stimulation of cytokines such as interferon-gamma, interferon-1beta, tumor necrosis factor alpha or bacteria compounds such as lipopolysaccharides. Procalcitonin (PCT) levels