title: Comparative effects of heme and metalloporphyrins on interferon-gamma-mediated pathways in monocytic cells (THP-1).
abstract: Previous results have demonstrated links between cell-mediated immunity, interferon (IFN)-gamma and neopterin production with heme, porphyrins, and iron metabolism. In this study, we compared the effects of heme, several metalloporphyrins, protoporphyrin IX, and iron on the signal or IFN-gamma-mediated pathways, such as the expression of major histocompatibility complex class II antigens, neopterin formation, and the degradation of tryptophan. Using the human monocytic cell line, THP-1, we found that heme, Zn-mesoporphyrin, Zn-deuteroporphyrin, Co-protoporphyrin, and iron reduced the efficiency of the IFN-gamma signal. In addition, Zn-mesoporphyrin almost fully inhibited IFN-gamma-induced degradation of tryptophan by the heme protein, indoleamine 2,3-dioxygenase. In contrast, tin-protoporphyrin enhanced the IFN-gamma effects as seen by increased neopterin production, enhanced tryptophan degradation, and elevated HLA-DR antigen expression on cells. These effects are considered to be due to the action of heme, metalloporphyrins, iron, or heme byproducts on the IFN-gamma signal, rather than to direct effects on IFN-gamma-induced enzymatic pathways. Heme and metalloporphyrins were previously shown to affect heme oxygenase activity, T cell growth, and lipid peroxidation and to modulate interleukin 2 activity. These pathways are also known to be influenced by IFN-gamma, and our data suggest that heme and metalloporphyrins may directly modulate the efficiency of the IFN-gamma signal.
authors.affiliation: Institute for Medical Chemistry and Biochemistry, University of Innsbruck, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Weiss
authors.forename: J D
authors.initials: JD
authors.lastname: Lutton
authors.forename: D
authors.initials: D
authors.lastname: Fuchs
authors.forename: G
authors.initials: G
authors.lastname: Werner-Felmayer
authors.forename: G
authors.initials: G
authors.lastname: Bock
authors.forename: N G
authors.initials: NG
authors.lastname: Abraham
authors.forename: A
authors.initials: A
authors.lastname: Kappas
authors.forename: R D
authors.initials: RD
authors.lastname: Levere
authors.forename: H
authors.initials: H
authors.lastname: Wachter
mesh_terms: D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism; D006684:HLA-DR Antigens / Q000096:biosynthesis*; D006418:Heme / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D007948:Leukemia, Monocytic, Acute; D008665:Metalloporphyrins / Q000494:pharmacology*; D019798:Neopterin; D011994:Recombinant Proteins; D014364:Tryptophan / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D006684:HLA-DR Antigens; D008665:Metalloporphyrins; D011994:Recombinant Proteins; D001708:Biopterins; D006418:Heme; D019798:Neopterin; D007371:Interferon-gamma; D014364:Tryptophan; D014366:Tryptophan Oxygenase