Hara Toshiaki, Ogasawara Nanako, Akimoto Hidetoshi, Takikawa Osamu, Hiramatsu Rie, Kawabe Tsutomu, Isobe Ken-Ichi, Nagase Fumihiko
Department of Medical Technology, Nagoya University School of Health Sciences, 1-20 Daikominami-1-chome, Higashi-ku, Nagoya, Aichi, 461-8673, Japan.
Immunol Lett. 2008 Feb 15;116(1):95-102. doi: 10.1016/j.imlet.2007.11.016. Epub 2007 Dec 26.
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.
在某些树突状细胞（DC）中，如浆细胞样DC（pDC），吲哚胺2,3-双加氧酶（IDO）启动的沿犬尿氨酸（Kyn）途径的色氨酸代谢调节T细胞反应。目前尚不清楚骨髓来源的髓样DC（BMDC）是否表达功能性IDO。使用GM-CSF从小鼠骨髓细胞分化出的CD11c(+)CD11b(+) BMDC中检测IDO表达。在培养24小时的BMDC中，CpG寡脱氧核苷酸（CpG）诱导IDO蛋白表达并产生一氧化氮（NO）。在使用BMDC细胞提取物的酶测定中，添加一氧化氮合酶（NOS）抑制剂可增强CpG刺激的BMDC的IDO活性，这表明IDO活性受到NO产生的抑制。另一方面，CpG刺激并未增加BMDC培养上清液中Kyn的浓度。外源性添加的Kyn被BMDC摄取，与CpG刺激和NO产生无关，并且Kyn的摄取受到转运系统L特异性抑制剂或高浓度色氨酸的抑制。BMDC对色氨酸的摄取明显低于对Kyn的摄取。总之，BMDC中的IDO活性受NO产生的下调，而BMDC强烈摄取外源性Kyn。
