Neopterin formation and tryptophan degradation by a human myelomonocytic cell line (THP-1) upon cytokine treatment.
Determination of neopterin [D-erythro-6-(1',2',3'-trihydroxypropyl)pterin] in body fluids is a powerful diagnostic tool in a variety of diseases in which activation of cellular immune mechanisms is involved, such as certain malignancies, allograft rejection, and autoimmune and infectious diseases. In vitro, neopterin is released into the supernatant by peripheral blood-derived monocytes/macrophages upon stimulation with gamma-interferon. In parallel, cleavage of tryptophan by indoleamine 2,3-dioxygenase is induced. We report here that the human myelomonocytic cell line THP-1 forms neopterin and degrades tryptophan upon treatment with gamma-interferon. Like in macrophages alpha-interferon and beta-interferon induce these pathways only to a much smaller degree. The action of interferons is enhanced by cotreatment with tumor necrosis factor alpha, lipopolysaccharide, or dexamethasone. gamma-Interferon-induced neopterin formation and indoleamine 2,3-dioxygenase activity are increased by raising extracellular tryptophan concentrations. The pattern of intracellularly formed pteridines upon stimulation with gamma-interferon shows the unique characteristics of human monocytes/macrophages. Neopterin, monapterin, and biopterin are produced in a 50:2:1 ratio. Thus, the THP-1 cell line provides a permanent, easily accessible in vitro system for studying the induction and mechanism of neopterin formation.
Werner-Felmayer
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G
Institute for Medical Chemistry and Biochemistry, University of Innsbruck, Austria.
Werner
E R
ER
Fuchs
D
D
Hausen
A
A
Reibnegger
G
G
Wachter
H
H
D001708:Biopterins / Q000031:analogs & derivatives* / Q000096:biosynthesis; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D019798:Neopterin; D011994:Recombinant Proteins; D014364:Tryptophan / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000096:biosynthesis*
D007370:Interferon Type I; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D001708:Biopterins; D019798:Neopterin; D003907:Dexamethasone; D007371:Interferon-gamma; D014364:Tryptophan; D014366:Tryptophan Oxygenase