Skip to main content
SpringerLink
Log in

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

  • Full Paper
  • Published:
Amino Acids Aims and scope Submit manuscript

Summary

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-γ (IFN-γ) stimulation. The regulation of IDO expression appears to differ in the two cell lines. Nitric oxide (NO) production negatively modulates the expression of IDO activity in IFN-γ-primed macrophages, thereby indicating a cross-talk between the kynurenine and nitridergic pathways in these cells. Conversely, this down-regulation of IDO activity by NO does not occour in microglial cells. A differential regulation of IDO expression in the two cell lines was also observed with LPS and picolinic acid. Together with previous findings, these results indicate the existence of marked differences in the regulation of the expression of the kynurenine pathway enzymes between macrophages and microglial cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

IFN-γ :

interferon-γ

IDO:

indoleamine 2,3-dioxygenase

NO:

nitric oxide

iNOS:

inducible nitric oxide synthase

NAME:

N-(ω))-nitro-L-arginine methyl ester

SMTC:

S-methyl-L-thiocitrulline

BNI:

3-bromo-7-nitroindazole

PIC:

picolinic acid

IL:

interleukin

References

  • Alberati-Giani D, Ricciardi-Castagnoli P, Köhler C, Cesura AM (1996) Regulation of the kynurenine metabolic pathway by interferon-y in murine cloned macrophages and microglial cells. J Neurochem 66: 996–1004

    Google Scholar 

  • Alberati-Giani D, Mahlerbe P, Ricciardi-Castagnoli P, Köhler C, Denis-Donini S, Cesura AM (1997) Differential regulation of indoleamine 2,3-dioxygenase expression by nitric oxide and inflammatory mediators in IFN-γ-activated murine macrophages and microglial cells. J Immunol 159: 419–426

    Google Scholar 

  • Blight AR, Cohen TI, Saito, K, Heyes, MP (1995) Quinolinic acid accumulation and functional deficits following experimental spinal cord injury. Brain 118: 735–752

    Google Scholar 

  • Habara-Ohkubo A, Takikawa O, Yoshida R (1991) Cloning and expression of a cDNA encoding mouse indoleamine 2,3-dioxygenase. Gene 105: 221–227

    Google Scholar 

  • Heyes MP, Saito K, Major EO, Milstein S, Markey SP, Vickers JH (1993) A mechanism of quinolinic acid formation by brain in inflammatory neurological disease. Brain 116: 1425–1450

    Google Scholar 

  • Hu B, Hissong BD, Carlin JM (1995) Interleukin-1 enhances indoleamine 2,3-dioxygenase activity by increasing specific mRNA expression in human mononuclear phagocytes. J Interferon Cytokine Res 15: 617–624

    Google Scholar 

  • Landolfo S, Garotta G (1991) IFN-γ, a lymphokine that modulates immunological and inflammatory responses. J Immunol Res 3: 81–94

    Google Scholar 

  • Lutz MB, Granucci F, Winzler C, Marconi G, Paglia P, Foti M, Assmann CU, Cirns L, Resigno M, Ricciardi-Castagnoli P (1994) Retroviral immortalization of phagocytic and dendritic cell clones as a tool to investigate funtional heterogeneity. J Immunol Meth 174: 269–279

    Google Scholar 

  • Melillo G, Cox GW, Biragyin A, Sheffler LA, Varesio L (1994) Regulation of nitric-oxide synthase mRNA expression by interferon-γ and picolinic acid. J Biol Chem 269: 8128–8133

    Google Scholar 

  • Moncada S, Palmer R M J, Higgs E A (1991) Nitric oxide: physiology pathophysiology, and pharmacology. Pharmacol Rev 43: 109–142

    Google Scholar 

  • Musso T, Gusella GL, Brooks A, Longo DL, Varesio L (1994) Interleukin-4 inhibits indoleamine 2,3 dioxygenase expression in human monocytes. Blood 83: 1408–1411

    Google Scholar 

  • Okuda S, Nishiyama N, Saito H, Katsuki H (1996) Hydrogen peroxide-mediated neuronal cell death induced by an endogenous neurotoxin, 3-hydroxykynurenine. Proc Natl Acad Sci USA 93: 12553–12558

    Google Scholar 

  • Rutheford MS, Witsell A, Schook LB (1993) Mechanism generating functionally heterogeneous macrophages: chaos revisited. J Leukoc Biol 53: 602–618

    Google Scholar 

  • Sassano M, Granucci F, Seveso M, Marconi G, Foti M, Ricciardi-Castagnoli P (1994) Molecular cloning of a recombinant retrovirus carrying a mutated envAKR-mycMH2 fusion gene immortalizing cells of the monocytec-macrophage lineage. Oncogene 9: 1473–1477

    Google Scholar 

  • Takikawa O, Koroiwa T, Yamazaki F, Kido R (1988) Mechanism of interferon-yaction. Characterization of indoleamine 2,3-dioxygenase in cultured human cells induced by interferon-γ and evaluation of the enzyme-mediated tryptophan degradation in its anticellular activity. J Biol Chem 263: 2041–2048

    Google Scholar 

  • Taylor MW, Feng G (1991) Relationship between interferon-γ, indoleamine 2,3-dioxygenase, and tryptophan catabolism. FASEB J 5: 2516–2552

    Google Scholar 

  • Thomas SR, Mohr D, Stocker R (1994) Nitric oxide inhibits indoleamine 2,3-dioxygenase activity in interferon-γ-primed mononuclear phagocytes. J Biol Chem 269: 14457–14464

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pharma Division, Preclinical Research, Nervous System Diseases, F. Hoffmann La Roche Ltd, PRPN (70/307b), CH-4070, Basel, Switzerland

    D. Alberati-Giani & A. M. Cesura

Authors
  1. D. Alberati-Giani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. M. Cesura
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Alberati-Giani, D., Cesura, A.M. Expression of the kynurenine enzymes in macrophages and microglial cells: regulation by immune modulators. Amino Acids 14, 251–255 (1998). https://doi.org/10.1007/BF01345271

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01345271

Keywords

Search

Navigation