Expression of the kynurenine enzymes in macrophages and microglial cells: regulation by immune modulators.

The regulation of the expression of indoleamine 2,3-dioxygenase (IDO) was studied in cloned murine macrophages (MT2) and microglial (N11) cells. Both cell lines express IDO and inducible nitric oxide synthase activity after interferon-gamma (IFN-gamma) stimulation. The regulation of IDO expression appears to differ in the two cell lines.

Differential regulation of indoleamine 2,3-dioxygenase expression by nitric oxide and inflammatory mediators in IFN-gamma-activated murine macrophages and microglial cells.

Induction of indoleamine 2,3-dioxygenase (IDO) and nitric oxide synthase (NOS) is involved in the immunomodulatory roles of IFN-gamma and evidence suggests that these pathways are functionally cross-regulated. We report here that nitric oxide (NO) negatively modulates the expression of IDO activity in IFN-gamma-primed macrophages, but not in microglial cells from mouse. In MT2 macrophages, the induction of IDO activity by IFN-gamma was further increased by the presence of NOS inhibitors, whereas culturing of IFN-gamma-activated MT2 cells with NO generators produced a marked reduction of IDO activity expression.

Cloning and functional expression of human kynurenine 3-monooxygenase.

Kynurenine 3-monooxygenase, an NADPH-dependent flavin monooxygenase, catalyses the hydroxylation of L-kynurenine to L-3-hydroxykynurenine. By hybridization screening using a cDNA probe encoding the entire exon 2 of Drosophila melanogaster kynurenine 3-monooxygenase, we isolated a 2.0 kb cDNA clone coding for the corresponding human liver enzyme.

Isolation and expression of a cDNA clone encoding human kynureninase.

Kynureninase (L-kynurenine hydrolase), a pyridoxal-5'-phosphate-(pyridoxal-P)-dependent enzyme, catalyses the cleavage of L-kynurenine and L-3-hydroxykynurenine into anthranilic and 3-hydroxyanthranilic acids, respectively. In this report, we describe the isolation of a cDNA clone encoding human kynureninase. Degenerate oligonucleotides designed from the amino acid sequences of peptides from rat liver kynureninase, were used as primers for reverse-transcription PCR of rat kidney RNA.

Regulation of the kynurenine metabolic pathway by interferon-gamma in murine cloned macrophages and microglial cells.

Several pieces of evidence suggest a major role for brain macrophages in the overproduction of neuroactive kynurenines, including quinolinic acid, in brain inflammatory conditions. In the present work, the regulation of kynurenine pathway enzymes by interferon-gamma (IFN-gamma) was studied in immortalized murine macrophages (MT2) and microglial (N11) cells. In both cell lines, IFN-gamma induced the expression of indoleamine 2,3-dioxygenase (IDO) activity.