High-affinity uptake of kynurenine and nitric oxide-mediated inhibition of indoleamine 2,3-dioxygenase in bone marrow-derived myeloid dendritic cells.
Indoleamine 2,3-dioxygenase (IDO)-initiated tryptophan metabolism along the kynurenine (Kyn) pathway in some dendritic cells (DC) such as plasmacytoid DC (pDC) regulates T-cell responses. It is unclear whether bone marrow-derived myeloid DC (BMDC) express functional IDO. The IDO expression was examined in CD11c(+)CD11b(+) BMDC differentiated from mouse bone marrow cells using GM-CSF. CpG oligodeoxynucleotides (CpG) induced the expression of IDO protein with the production of nitric oxide (NO) in BMDC in cultures for 24h. In the enzyme assay using cellular extracts of BMDC, the IDO activity of BMDC stimulated with CpG was enhanced by the addition of a NO synthase (NOS) inhibitor, suggesting that IDO activity was suppressed by NO production. On the other hand, the concentration of Kyn in the culture supernatant of BMDC was not increased by stimulation with CpG. Exogenously added Kyn was taken up by BMDC independently of CpG stimulation and NO production, and the uptake of Kyn was inhibited by a transport system L-specific inhibitor or high concentrations of tryptophan. The uptake of tryptophan by BMDC was markedly lower than that of Kyn. In conclusion, IDO activity in BMDC is down-regulated by NO production, whereas BMDC strongly take up exogenous Kyn.
Hara
Toshiaki
T
Department of Medical Technology, Nagoya University School of Health Sciences, 1-20 Daikominami-1-chome, Higashi-ku, Nagoya, Aichi, 461-8673, Japan.
Ogasawara
Nanako
N
Akimoto
Hidetoshi
H
Takikawa
Osamu
O
Hiramatsu
Rie
R
Kawabe
Tsutomu
T
Isobe
Ken-Ichi
K
Nagase
Fumihiko
F
D000818:Animals; D001853:Bone Marrow / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D004705:Endocytosis; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism*; D007737:Kynurenine / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D051379:Mice; D022423:Myeloid Cells / Q000378:metabolism*; D009569:Nitric Oxide / Q000276:immunology / Q000378:metabolism*; D010587:Phagocytosis; D015398:Signal Transduction
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D009569:Nitric Oxide; D007737:Kynurenine