Differential effect of type I and type II interferons on neopterin production and amino acid metabolism in human astrocyte-derived cells.
Intrathecal production of neopterin, a pteridine produced by interferon (IFN)-gamma-stimulated monocyte-derived macrophages, is associated with neurological disorders and infections. We investigated whether IFN-alpha/beta, IFN-gamma, or human immunodeficiency virus (HIV) induce neopterin production by human astroglioma cells. IFN-alpha/beta and IFN-gamma, but not HIV, induced neopterin. Interestingly, IFN-gamma, but not IFN-alpha/beta, increased expression and activity of the tryptophan-catabolizing enzyme indoleamine (2,3)-dioxygenase. In contrast, IFN-alpha/beta, but not IFN-gamma, reduced the uptake of three aromatic amino acids in U87MG and U138 astroglioma cells. Thus type I and type II IFN stimulate astrocyte-derived cells to produce neopterin and exert differential effects on amino acid metabolism.
Cano
Oscar D
OD
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
Neurauter
Gabriele
G
Fuchs
Dietmar
D
Shearer
Gene M
GM
Boasso
Adriano
A
D015526:AIDS Dementia Complex / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D024322:Amino Acids, Aromatic / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000821:virology; D045744:Cell Line, Tumor; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000187:drug effects / Q000378:metabolism; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D019798:Neopterin / Q000096:biosynthesis* / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism
D024322:Amino Acids, Aromatic; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016898:Interferon-alpha; D019798:Neopterin; D007371:Interferon-gamma; D014364:Tryptophan