Comparative Effects of Heme and Metalloporphyrins on Interferon- -Mediated Pathways in Monocytic Cells (THP-1)

Autor: Dietmar Fuchs, Richard D. Levere, Günter Weiss, Attallah Kappas, Helmut Wachter, Nader G. Abraham, J. D. Lutton, Gunter Bock, Gabriele Werner-Felmayer
Rok vydání: 1993
Předmět:
Zdroj: Experimental Biology and Medicine. 202:470-475
ISSN: 1535-3699
1535-3702
DOI: 10.3181/00379727-202-43561
Popis: 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.
Databáze: OpenAIRE