Indoleamine 2,3-Dioxygenase Participates in the Interferon-gamma-Induced Cell Death Process in Cultured Bovine Luteal Cells

Abstract Interferon-gamma (IFNG) induces apoptotic cell death in bovine luteal cells, but the pathway(s) involved in this process are not well defined. Evidence supporting the involvement of an IFNG-inducible enzymatic pathway that degrades tryptophan in IFNG-induced death of bovine luteal cells is presented in this study. The IFNG-inducible enzyme indoleamine 2,3-dioxygenase (INDO) catalyzes the first step in a metabolic pathway that degrades tryptophan. In the first experiment, RT-PCR revealed the presence of INDO mRNA in luteal cells treated with IFNG, but not in untreated cells. To determine whether INDO participates in IFNG-induced death of bovine luteal cells, an experiment was performed to test the effect of 1-methyl-d-tryptophan (1-MT), an inhibitor of INDO, on IFNG-induced DNA fragmentation in luteal cells. Single-cell gel electrophoresis and microscopic image analysis revealed that 1-MT inhibited DNA fragmentation induced by IFNG. To determine whether supplementation of cell cultures with additi...