期刊
ENDOCRINOLOGY
卷 152, 期 12, 页码 4984-4992出版社
ENDOCRINE SOC
DOI: 10.1210/en.2011-0278
关键词
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资金
- Ministry of Health, Labor, and Welfare
- Ministry of Education, Culture, Sports, Science, and Technology
- Japan China Medical Association
- National Natural Science Foundation of China
- Yamaguchi Endocrine Research Foundation
- Japan Society for the Study of Hypertension in Pregnancy
- Inohana Alumni Association of Chiba University School of Medicine
- Grants-in-Aid for Scientific Research [23890045, 23592396] Funding Source: KAKEN
Indoleamine 2,3-dioxygenase (IDO) is an enzyme that degrades an essential amino acid, tryptophan, and plays a role in inhibiting the proliferation of T cells and intracellular pathogens. Inhibiting IDO in mice leads to fetal rejection, suggesting its significance in establishing pregnancy. Toll-like receptor 3 (TLR-3) is a key component of the innate immune system that recognizes viral double-stranded RNA and triggers immune reactions by producing type I interferon. Using a human trophoblast cell culture system, we studied the effect of TLR-3 ligation on IDO expression and function by treating trophoblasts with polyinosinic-polycytidylic acid [poly(I:C)] (a synthetic double stranded RNA, which mimics viral RNA). Real-time PCR and Western blot analysis revealed that IDO mRNA and protein expression was significantly induced by poly(I:C). The activity of IDO was also increased by poly(I:C) given that the L-kynurenine concentrations were elevated in conditioned media. Conditioned media from poly(I:C)-treated trophoblasts were found to inhibit the proliferation of human T cells significantly. Poly(I:C) was also shown to induce interferon (IFN)-beta mRNA expression in trophoblasts. Recombinant human IFN-beta increased IDO mRNA expression in trophoblasts more rapidly than poly(I:C). Pretreating with neutralizing antibody against IFN-beta significantly suppressed IDO induction by poly(I:C). Collectively we have demonstrated that ligation of TLR-3 by poly(I:C) induces IDO expression in human first-trimester trophoblasts via an IFN-beta-dependent pathway. These findings suggest that upon viral infection, trophoblasts induce IDO and in turn contribute to antimicrobial activity and maintenance of fetomaternal tolerance. (Endocrinology 152: 4984-4992,2011)
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