Expression of indoleamine 2,3-dioxygenase and production of quinolinic acid by human microglia, astrocytes, and neurons.
There is good evidence that the kynurenine pathway (KP) and one of its end products, quinolinic acid (QUIN) play a role in the pathogenesis of several major neurological diseases. While QUIN has been shown to be produced in neurotoxic concentrations by macrophages and microglia, the capacity of astrocytes and neurons to produce QUIN is controversial. Using interferon gamma (IFN-gamma)-stimulated primary cultures of human mixed brain cells, we assayed expression of the KP regulatory enzyme indoleamine 2,3-dioxygenase (IDO) and QUIN production by immunocytochemistry. Using IFN-gamma-stimulated purified cultures of neurons, astrocytes, microglia and macrophages, we studied IDO expression by RT-PCR and production of QUIN using mass spectrometry. We found that astrocytes, neurons, and microglia expressed IDO but only microglia were able to produce detectable amounts of QUIN. However, astrocytes and neurons had the ability to catabolize QUIN. This study also provides the first evidence of IDO expression and lack of production of QUIN in culture of primary human neurons.
Guillemin
Gilles J
GJ
Centre for Immunology, St. Vincent's Hospital, Sydney, Australia. g.guillemin@cfi.unsw.edu.au
Smythe
George
G
Takikawa
Osamu
O
Brew
Bruce J
BJ
D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism; D001923:Brain Chemistry / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004660:Encephalitis / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma / Q000494:pharmacology; D007737:Kynurenine / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013058:Mass Spectrometry; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015394:Molecular Structure; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017378:Quinolinic Acid / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014366:Tryptophan Oxygenase / Q000378:metabolism*
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D007371:Interferon-gamma; D014366:Tryptophan Oxygenase; D017378:Quinolinic Acid