Hepatitis B, Chronic ; immunology ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; immunology

Cell Adhesion ; Cell Movement ; Cell Proliferation ; Hep G2 Cells ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; genetics ; Transfection

Immune thrombocytopenia (ITP) is a common acquired autoimmune hematological disorders. Platelet autoantibodies lead to the decrease of platelet production and (or) increase of its destruction. The latest researches showed that the abnormal tryptophan metabolism mediated by indoleamine-2, 3-dioxygenase(IDO) is related with the pathogenesis of ITP. The patients with ITP show less expression of IDO, reduction of Treg cells and increase of autoreactive T cells and autoantibodies. CTLA-4-Ig can improve the expression of IDO in the patients with ITP, which also can inhibit the proliferation and activation of self-reactive T cells. Thus, clarifying the abnormal tryptophan metabolism mediated by IDO may provide a new idea for improving the understand of the pathogenesis and treatment of ITP. This review focuses on reasearch progress of the tryptophan metabolism mediated by IDO and ITP.
Autoantibodies ; Blood Platelets ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; Thrombocytopenia ; Thrombopoiesis ; Tryptophan

Munn et al. made a scientific observation of major biological importance. For the first time they showed that in the mammal the fetus does survive an immune attack mounted by the mother, and that the mechanism responsible for the survival depends on the fetus and placenta 'actively' defending itself from attack by maternal T cells by means of an enzyme indoleamine 2,3-dioxygenase (EC 1.13.11.42) dependent localised depletion of L-tryptophan. These findings raise critical questions for disease and its prevention during human pregnancy. Specifically, the role of this mechanism (discovered in mouse) in the human, and the extent to which defective activation of this process is responsible for major clinical diseases are unknown. Therefore some key facts about this enzyme expressed in the human placenta have been studied in order to test whether Munn et al.'s findings in mouse are met for human pregnancy. This short review attempts to describe our experimental work on human placental indoleamine 2,3-dioxygenase.
Animals ; Fetus ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; Mammals ; Mice ; Mothers ; Placenta ; Pre-Eclampsia ; Pregnancy ; T-Lymphocytes ; Tryptophan

PURPOSE: To identify the localization of indoleamine 2,3-dioxygenase (IDO) in human corneal cells and to evaluate its ability to act as a local immunosuppressive factor. METHODS: The expression profile of IDO was obtained with RT-PCR and Western blot of in a primary culture of human corneal cells (fibroblasts, epithelial cells and endothelial cells). In order to investigate the immunosuppressive function of IDO, immune cells were cultured in a human corneal cell-conditioned medium, and their prolifleration was identified by the MTT assay. Moreover, apoptotic effects of IDO in immune cells treated with IFN-gamma were also investigated with apoptosis ELISA. RESULTS: Among the three different types of human corneal cells analyzed, mRNA and protein expression of IDO was observed only in human corneal fibroblasts. Immune cells cultured in a human corneal fibroblast-conditioned medium showed inhibited proliferation. Moreover, IFN-gamma-induced expression of IDO significantly enhanced apoptotic ability in a dose-depandant manner. CONCLUSIONS: Our results suggest that human corneal fibroblasts are relatively immuno-resistant and that expression of IDO may be one of the factors involved in the immune tolerance observed in corneal grafts.
Apoptosis ; Blotting, Western ; Enzyme-Linked Immunosorbent Assay ; Epithelial Cells ; Fibroblasts ; Humans* ; Immune Tolerance ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; RNA, Messenger ; Transplants

OBJECTIVETo review the recent studies about the role of indoleamine 2,3-dioxygenase (IDO) in tumor induced tolerance.

DATA SOURCESPublished articles (1978 - 2009) on IDO and tumor induced tolerance were selected from Medline.

STUDY SELECTIONArticles selected were relevant to development of IDO in tumor induced tolerance. Of all originally identified articles, 50 specially addressed the stated purpose.

RESULTSRecent work has revealed IDO at high levels in tumors and in tumor-draining lymph nodes and a close relationship between IDO activity and the regulatory T cells.

CONCLUSIONUp-regulation of IDO is proven to be a mechanism of acquired tolerance in tumors, in which the closely coupled positive feedback system between IDO and regulatory T cells may be considered to play an important role.

Animals ; Gene Expression Regulation, Neoplastic ; physiology ; Humans ; Immune Tolerance ; physiology ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; metabolism ; Neoplasms ; enzymology ; immunology

In order to confirm the existence of indoleamine 2, 3-dioxygenase (IDO) gene in swine, and to clone the novel gene followed by the molecule structure properties and expression pattern analysis, the porcine mRNA sequences homologous to human IDO were obtained from GenBank database by bioinformatics method. By using RT-PCR, the IDO gene was cloned from porcine endothelial cell line and the accuracy of the nucleic acid sequence was confirmed, and the expression pattern of the gene was detected. The three-dimensional structure model of porcine IDO was built referring to the tertiary structure of human IDO using biological sequence analysis software and database. The results showed that the porcine IDO was identified by sequencing. The nucleotide sequences were confirmed as a novel gene after submitted to Genbank. Porcine IDO was expressed in the lung, thymus, epididymis and anterior chamber with a basic level, however in peripheral blood mononuclear cells (PBMCs) the IDO gene was highly expressed. The three-dimensional structure model of porcine IDO was similar to that of human IDO. It was suggested that identification of the structure information of porcine IDO is essential to further investigate the immunologic function of the gene. Study of IDO on NK cells-mediated xenograft rejection will be a novel therapeutic target for the development of xenotransplantation.
Amino Acid Sequence ; Animals ; Base Sequence ; Cell Line ; Cloning, Molecular ; methods ; Endothelial Cells ; metabolism ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; genetics ; metabolism ; Molecular Sequence Data ; Sequence Alignment ; Swine

This study was aimed to investigate the mechanism of indoleamine 2, 3-dioxygenase (IDO) activity in acute myeloid leukemia cells contributing to tumor immune escape. Myeloid leukemia cells were isolated from bone marrow of 23 patients with acute myeloid leukemia (AML) and IDO expression was detected by immunochemistry and RT-PCR methods. Then mixed lymphocyte reaction (MLR) of one way was carried out, leukemia cells were used as stimulating cells and T-lymphocytes were used as reactive cells in culture with or without 1-MT. T-lymphocyte proliferation rate was determined by MTT assay and IDO activity in supernatant of MLR was detected by high-performance liquid chromatography (HPLC). The results showed that IDO expression was found in 17 out of 23 cases of acute myeloid leukemia cells; IDO enzyme activity in leukemia cells inhibited T-lymphocyte proliferation in MLR cultures. It is concluded that IDO activity expressing in leukemia cells can suppress T-lymphocyte proliferation responses, which may be contributing to tumor immune escape.
Cell Proliferation ; Humans ; Immune Tolerance ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; metabolism ; Leukemia, Myeloid, Acute ; enzymology ; immunology ; pathology ; T-Lymphocytes ; cytology ; immunology ; Tumor Cells, Cultured ; Tumor Escape ; immunology

Indoleamine 2,3-dioxygenases (IDOs) are tryptophan-catabolizing enzymes with immunomodulatory functions. However, the biological role of IDO2 and its relationship with IDO1 are unknown. To assess the relationship between IDO2 and IDO1, we investigated the effects of co-expression of human (h) IDO2 on hIDO1 activity. Cells co-expressing hIDO1 and hIDO2 showed reduced tryptophan metabolic activity compared with those expressing hIDO1 only. In a proteomic analysis, hIDO1-expressing cells exhibited enhanced expression of proteins related to the cell cycle and amino acid metabolism, and decreased expression of proteins related to cell survival. However, cells co-expressing hIDO1 and hIDO2 showed enhanced expression of negative regulators of cell apoptosis compared with those expressing hIDO1 only. Co-expression of hIDO1 and hIDO2 rescued the cell death induced by tryptophan-depletion through hIDO1 activity. Cells expressing only hIDO2 exhibited no marked differences in proteome profiles or cell growth compared with mock-transfectants. Cellular tryptophan metabolic activity and cell death were restored by co-expressing the hIDO2 mutant substituting the histidine 360 residue for alanine. These results demonstrate that hIDO2 plays a novel role as a negative regulator of hIDO1 by competing for heme-binding with hIDO1, and provide information useful for development of therapeutic strategies to control cancer and immunological disorders that target IDO molecules.
Cell Proliferation ; Cell Survival ; Gene Expression ; HEK293 Cells ; Heme/*metabolism ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics/*metabolism ; Protein Binding ; Tryptophan/*metabolism ; Up-Regulation

This study was aimed to investigate the effect of 1,25(OH)(2) vitamin D(3) [1,25(OH)(2) Vit D(3)] on the differentiation, maturation and function of human dendritic cells (DC) in vitro and its mechanism. Human peripheral blood mononuclear cells were induced to differentiate to DC in vitro. The DC in test group were cultured with 1,25(OH)(2) Vit D(3) 1 nmol/L for 9 d, while the DC in control group were cultured with the equivalent of absolute alcohol. The expression of co-stimulatory molecules on DC were analyzed by flow cytometry. T cell proliferation induced by DC was assessed by MTT method. The expression of indoleamine 2, 3-dioxygenase (IDO) protein was determined by Western blot. The results showed that compared with the control group, the expression of CD80, CD83 and CD86 on DC in test group was significantly down-regulated (P < 0.05), while the CD1a was up-regulated (P < 0.05). The expression rate of CD80, CD83, CD86, CD1a in test group were (40.43 ± 9.83)%, (20.04 ± 4.73)%, (14.45 ± 5.38)%, (58.48 ± 10.72)% respectively, while in control group were (29.36 ± 13.34)%, (35.91 ± 10.19)%, (27.15 ± 11.64)%, (72.20 ± 12.79)% respectively. Compared with the control group, 1,25(OH)(2) Vit D(3)-treated DC exhibited a markedly reduced ability to stimulate allogenic T cell proliferation and up-regulated IDO protein expression.It is concluded that 1,25(OH)(2) Vit D(3) efficiently inhibits the maturation of DC and DC-mediated T cell proliferation, which may be related to the up-regulation of IDO protein expression.
Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Cholecalciferol ; pharmacology ; Dendritic Cells ; cytology ; immunology ; Flow Cytometry ; Humans ; Immune Tolerance ; drug effects ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; metabolism