Guillemin GJ, Kerr SJ, Smythe GA, Armati PJ, Brew BJ.
J Neurovirol. 1998 Jun 3-6; 4: 352.
Centre for Immunology, St. Vincent's Hospital, Sydney, Australia.
Astrocytes are involved in various inflammatory brain diseases, including the AIDS dementia complex. However, their exact role in kynurenine pathway metabolism, particularly their capacity to produce quinolinic acid (QUIN), is poorly understood. In the present study, we investigated QUIN production by human fetal astrocytes after cytokine stimulation, and also determined effects of addition of QUIN or, the QUIN precursor, 3-hydroxyanthranilic acid (3HAA) on the expression of 3 major enzymes of the kynurenine pathway. QUIN or 3HAA were added to purified cultures of primary human fetal astrocytes which were stimulated with IL-1beta, IFN-gamma, IL-6, TNF-alpha or GM-CSF. QUIN concentrations were measured in culture supernatants after 72 hours using gas chromatography/mass spectrometry. Expression of indoleamine 2,3-dioxygenase (IDO), 3-hydroxyanthranilate dioxygenase (3-HAO) and quinolinate phosphoribosyltransferase (QPRTase) mRNA was determined using RT-PCR. Human fetal astrocytes have the capacity to produce a low level of QUIN (300 to 350nM), regardless of the presence of 3HAA in the culture medium. There were no variations in QUIN production in response to cytokine stimulation. However, expression of QPRTase mRNA was potentiated by cytokines, whereas 3-HAO was expressed even without cytokine stimulation. Addition of 1 micromolar QUIN in the astrocyte culture medium had an inhibitory effect on expression of 3-HAO. Human fetal astrocytes have a limited ability to synthesise QUIN. These results suggest that QUIN metabolic pathway is subject to complex regulatory mechanisms and QUIN production is probably an accessory pathway in astrocytes.
Publication Types:
Keywords:
- 3-Hydroxyanthranilic Acid
- AIDS Dementia Complex
- Animals
- Astrocytes
- Cytokines
- Fetus
- Humans
- Interleukin-1
- Interleukin-6
- Kynurenine
- Neurosciences
- Quinolinic Acid
- RNA, Messenger
- TNF protein, human
- Tumor Necrosis Factor-alpha
- metabolism
Other ID:
UI: 102237414
From Meeting Abstracts