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Role Of Ido Activation In Anti-Microbial Defense in Human Native Astrocytes

  • Claudia Oberdörfer
  • Ortwin Adams
  • Colin R. MacKenzie
  • J. A. De Corline
  • Groot Däubener
  • Walter Däubener
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 527)

Abstract

The most serious complication of human toxoplasmosis is the development of toxoplasmic encephalitis. It is well established that in the brainToxoplasma gondiiis able to replicate in microglial cells, astrocytes and neurons, and that all three cell types can harbor toxoplasma cysts. The role of astrocytes in the defense against toxoplasma is not clear. The most prominent effector-mechanisms against toxoplasma are the induction of the inducible form of the nitric oxide synthase (iNOS), and the induction of indoleamine 2,3-dioxygenase (IDO).

In this paper we show that interferon (IFN)-y-activated, native human astrocytes express IDO activity, as shown by the detection of IDO mRNA using RT-PCR, detection of enzyme expression with IDO-specific monoclonal antibodies in Western blots, as well as by direct measurement of enzyme activity in the activated cells. IFN-y—mediated IDO activity in human astrocytes inhibits the growth ofToxoplasma gondiiand of group B streptococci. Furthermore, we show for the first time that IFN-y induced IDO activity is also effective in inhibiting the growth of Herpes Simplex Virus in astrocyte cultures.

In addition, iNOS expression was detectable by RT-PCR in all batches of astrocytes tested when stimulated with a cytokine cocktail of IFN-y, TNF-a, IL-1 and LPS. Furthermore, we found that the amount of nitric oxide produced by astrocytes is not sufficient to inhibit either toxoplasmal or bacterial growth. Co-activation of iNOS and IDO on the other hand, results in an inhibition of IDO activity in astrocytes.

Keywords

Nitric Oxide Nitric Oxide Quinolinic Acid Astrocyte Culture Human Astrocyte 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Claudia Oberdörfer
  • Ortwin Adams
  • Colin R. MacKenzie
  • J. A. De Corline
  • Groot Däubener
  • Walter Däubener
    • 1
  1. 1.Institut für Medizinische Mikrobiologie und VirologieHeinrich-Heine UniversitätDüssddorfGermany

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