TY - JOUR
T1 - Indoleamine 2,3-dioxygenase is highly expressed in human adult T-cell leukemia/lymphoma and chemotherapy changes tryptophan catabolism in serum and reduced activity
AU - Hoshi, Masato
AU - Ito, Hiroyasu
AU - Fujigaki, Hidetsugu
AU - Takemura, Masao
AU - Takahashi, Takeshi
AU - Tomita, Eiichi
AU - Ohyama, Masami
AU - Tanaka, Ryo
AU - Saito, Kuniaki
AU - Seishima, Mitsuru
PY - 2009/1
Y1 - 2009/1
N2 - Adult T-cell leukemia/lymphoma (ATLL) is caused by human T-cell lymphotropic virus type 1 (HTLV-1). Indoleamine 2,3-dioxygenase (IDO), the l-tryptophan (l-TRP)-degrading enzyme, plays a key role in the powerful immunomodulatory effects of several different types of immune cells. In this study, we investigated the IDO expression in ATLL cells and the effect of chemotherapy on IDO-initiating l-TRP catabolism in patients with ATLL. Serum l-kynurenine (l-KYN) concentrations, l-KYN/l-TRP ratio, and the level of IDO mRNA expression in ATLL cells were significantly increased in ATLL patients compared to those in healthy and HTLV-positive carrier subjects. On the other hand, l-TRP level was significantly decreased in ATLL patients compared to that in healthy subjects. In the immunohistochemical staining, IDO was strongly expressed in cytoplasm of ATLL cells. Interestingly, serum l-KYN as well as soluble IL-2 receptor concentrations was significantly reduced, and l-TRP concentrations were significantly increased after chemotherapy. These data provide evidence that IDO is highly expressed in ATLL cells, and that IDO-initiating l-TRP catabolism changes with chemotherapy.
AB - Adult T-cell leukemia/lymphoma (ATLL) is caused by human T-cell lymphotropic virus type 1 (HTLV-1). Indoleamine 2,3-dioxygenase (IDO), the l-tryptophan (l-TRP)-degrading enzyme, plays a key role in the powerful immunomodulatory effects of several different types of immune cells. In this study, we investigated the IDO expression in ATLL cells and the effect of chemotherapy on IDO-initiating l-TRP catabolism in patients with ATLL. Serum l-kynurenine (l-KYN) concentrations, l-KYN/l-TRP ratio, and the level of IDO mRNA expression in ATLL cells were significantly increased in ATLL patients compared to those in healthy and HTLV-positive carrier subjects. On the other hand, l-TRP level was significantly decreased in ATLL patients compared to that in healthy subjects. In the immunohistochemical staining, IDO was strongly expressed in cytoplasm of ATLL cells. Interestingly, serum l-KYN as well as soluble IL-2 receptor concentrations was significantly reduced, and l-TRP concentrations were significantly increased after chemotherapy. These data provide evidence that IDO is highly expressed in ATLL cells, and that IDO-initiating l-TRP catabolism changes with chemotherapy.
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U2 - 10.1016/j.leukres.2008.05.023
DO - 10.1016/j.leukres.2008.05.023
M3 - Article
C2 - 18639341
AN - SCOPUS:55049112968
SN - 0145-2126
VL - 33
SP - 39
EP - 45
JO - Leukemia Research
JF - Leukemia Research
IS - 1
ER -
