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J Yodoi

Publications and source records attributed to J Yodoi.

At least 145 records · Page 8Linked to original sources
PubMed1995

Activation of natural killer cells by the mAb YTA-1 that recognizes leukocyte function-associated antigen-1.

The mAb YTA-1, which brightly stains CD3-CD16+ large granular lymphocytes (LGL)/natural killer (NK) cells and CD8+ T cells by immunofluorescence, is specific for leukocyte function-associated antigen (LFA)-1. Some mAbs recognizing the LFA-1 alpha chain (CD11a) or LFA-1 beta chain (CD18) inhibited the binding of YTA-1 to peripheral blood mononuclear cells. YTA-1 mAb could be chemically cross-linked to 170 and 96 kDa molecules, whose molecular weights correspond to those of LFA-1 alpha and beta respectively. YTA-1 bound to COS-7 cells co-transfected with CD11a and CD18 cDNAs, but not to untransfected cells. Reactivities of YTA-1 to K562 cells transfected with LFA-1 alpha and beta (CD11a/CD18) cDNAs and to CHO cells transfected with Mac-1 (CD11b/CD18) or p150, 95 (CD11c/CD18) cDNAs strongly suggest that YTA-1 recognizes either LFA-1 alpha or an epitope formed by a combination of LFA-1 alpha and beta. Treatment of fresh CD3-CD16+ LGL with YTA-1 augmented cytolytic activity and induced proliferation. F(ab')2 fragments of YTA-1 augmented NK cytotoxicity, indicating that the NK activating signal was transmitted through LFA-1 without involvement of Fc gamma receptor III. In contrast, the other mAbs against LFA-1 could not activate NK cells. These results collectively indicate that YTA-1 recognizes a unique epitope of LFA-1, which is involved in activation of fresh NK cells.

Animals↗
PubMed1995

Suppression of adult T cell leukemia-derived factor/human thioredoxin induction by FK506 and cyclosporin A: a new mechanism of immune modulation via redox control.

Adult T cell leukemia-derived factor (ADF), which is identical to a disulfide reducing enzyme human thioredoxin (TRX), is produced and released by activated or virus-infected lymphocytes. Here we report that, in peripheral blood mononuclear cells (PBMC) stimulated with phytohemagglutinin (PHA), ADF/TRX mRNA was induced within 8 h after stimulation as detected by in situ hybridization study. To analyze the mechanism of ADF/TRX induction during T cell activation, the effects of immunosuppressants including FK506, rapamycin (Rap) and cyclosporin A (CsA) on ADF/TRX expression were investigated by immunoblot analysis. ADF/TRX induction in PBMC by PHA, Con A or OKT3 mAb was almost completely suppressed by FK506. Whereas CsA also inhibited ADF/TRX expression in OKT3 mAb-stimulated PBMC, Rap failed to affect it in spite of exhibiting growth inhibition. In addition, exogenous IL-2 could not increase ADF/TRX production in FK506-treated PBMC or in PHA blasts. These results indicate that ADF/TRX induction in T cell activation depends on calcineurin-dependent events in the early phase and that IL-2 production is not directly involved in ADF/TRX induction. Furthermore, when recombinant ADF (rADF) was added to a culture of PBMC 1 h before the addition of PHA and FK506, the action of FK506 was partially reversed as determined by [3H]thymidine incorporation and viable cell counts. These results suggest that ADF/TRX produced and released from PBMC may be a crucial event in lymphocyte activation, and that FK506 and CsA may exert the immune suppression partly through inhibiting the induction of the endogenous reducing factor ADF/TRX.

Adjuvants, Immunologic↗
PubMed1995

Serum levels of soluble CD23 in patients with bullous pemphigoid.

In this study, we tested the serum levels of soluble CD23 (sCD23) in 27 bullous pemphigoid (BP) patients and compared them with the disease activity. Soluble CD23 is the cleaved portion of the low affinity Fc receptor for IgE (Fc epsilon RII/CD23) which has an affinity for IgE and regulates IgE synthesis. Although bullous pemphigoid (BP) is a subepidermal blistering disease characterized by IgG class autoantibodies against the basement membrane of stratified squamous epithelia, several IgE-related phenomena have been reported. Recently, we have shown that Fc epsilon RII-expressing and IgE-bearing cells are detectable in the lesional skin and concluded that an IgE-Fc epsilon RII/CD23 system may be involved in the pathogenesis of this disease. The serum level of sCD23 in BP patients was significantly higher than healthy controls (p < 0.01). In 11 out of 12 patients, the alteration of serum sCD23 levels correlated well with the disease activity. Thus the serum level of sCD23 is useful as a new parameter for assessing the level of disease activity in BP. High levels of sCD23 may represent part of an IgE-mediated immune reaction which may play a role in the pathogenesis of BP.

Anti-Inflammatory Agents↗
PubMed1995

Attenuation of ischaemia reperfusion injury by human thioredoxin.

BACKGROUND: Active oxygen species are thought to play a part in ischaemia reperfusion injury. The ability of a novel agent, human thioredoxin (hTRX), to attenuate lung damage has been examined in a rat model of ischaemia reperfusion injury. METHODS: Twenty eight animals were studied. At thoracotomy the left main bronchus and the left main pulmonary artery were clamped for 75 minutes and the lung was then reperfused for 20 minutes. Phosphate buffered saline was administered intravenously to nine control animals and hTRX (30 micrograms/g body weight) was given intravenously to another group of nine animals. Two experiments were carried out. The first (Exp 1) was a time matched pair experiment (five treated, five controls), and the second (Exp 2) was performed under controlled conditions (four treated, four controls; temperature 25 degrees C, humidity 65%). In another 10 nonischaemic rats and those in Exp 1 biochemical measurements of lipid peroxide, superoxide dismutase, and glutathione peroxide levels were performed. RESULTS: In both experiments rats perfused with hTRX survived longer than controls. In Exp 1 the arterial oxygen tension (PaO2) on air in the hTRX group was higher at 20 minutes than at one minute after reperfusion. In Exp 2 PaO2 at 20 minutes was higher in the hTRX group than in the controls. Lipid peroxide, superoxide dismutase, and glutathione peroxide levels in the control group were higher than in the hTRX group and in the non-ischaemic groups. Histological examination showed less thickening and oedema of the alveolar walls in the hTRX group than in controls. CONCLUSIONS: These results suggest that hTRX is effective as a radical scavenger and can limit the extent of ischaemia reperfusion injury of the lungs of experimental animals.

Animals↗
PubMed1995

Rejection and expression of thioredoxin in transplanted canine lung.

Thioredoxin (TRX) production has been shown to be induced by a variety of stresses. In this study, we examined TRX expression in lung tissues after canine lung transplantation to determine whether it could be induced by allogenic stimulations and could be used to diagnose early rejection. Thirty-five adult mongrel dogs were used in all. In group A, 24 dogs underwent allotransplantation of the left lung with no immunosuppressant and were sacrificed at various times; 5 were sacrificed on postoperative day (POD) 1; 5 on POD 2; 7 on POD 3; and 7 on POD 5. In group B, 5 donor right lungs were used for negative control. In group C, 3 dogs underwent autotransplantation. In group D, 8 dogs underwent allotransplantation of the left lung with optimal immunosuppression and were sacrificed at POD 28. Lung tissues were stained with anti-TRX antibody, and the TRX high-producer (TRXh) cells in a randomly chosen field were counted as the index of TRX expression. In group A, the number of TRXh cells were as follows: 1.68 +/- 1.14 in grade 0; 4.87 +/- 1.07 in grade 1; 10.42 +/- 4.24 in grade 2; 27.34 +/- 17.96 in grade 3; and 50.90 +/- 17.36 in grade 4. In group B, the number of TRXh cells was 1.82 +/- 1.01. There was a significant difference between each rejection grade in group A and group B (p < 0.01), and we could observe TRXh cells in the early stage of rejection. These results suggest that analysis of TRXh cells in lung tissues may be useful in the early diagnosis of rejection.

Animals↗
PubMed1995

Cell cycle inhibition of HTLV-I transformed T cell lines by retinoic acid: the possible therapeutic use of thioredoxin reductase inhibitors.

Adult T cell leukemia derived factor (ADF), which was first reported as a cytokine-like factor produced by human T lymphotropic virus I (HTLV-I)-transformed T cells, is a human homologue of thioredoxin (TRX). ADF/TRX has multiple functions including growth promoting, antiapoptotic and radical scavenging activities, and is also involved in a wide variety of intracellular processes as a dithiol reducing agent in cooperation with the NADPH-TRX reductase system. In HTLV-1(+) T cell lines, HuT 102 and MT-2, which are ADF/TRX high producing cells, we found that the expression of ADF/TRX was dependent on the cell cycle and peaked at S phase. The reducing activity of ADF/TRX in these cells was also dependent on the cell cycle and elevated in S phase as determined by NADPH-dependent insulin degradation assay. Furthermore, inhibitors of TRX reductase, 13-cis-retinoic acid (13-cis-RA) and azelaic acid, inhibited the DNA synthesis of these cells. In contrast, the residual expression and reducing activity of ADF/TRX in HTLV-I(-) T cell lines did not show any significant correlation with the cell cycle. There was no distinct inhibitory effect of 13-cis-RA or azelaic acid on the growth of these ADF/TRX low producing cells. These results indicate that a high level of reducing activity of the ADF/TRX system may be required for the cell division of these virally transformed cells. This suggests that the TRX reductase inhibitors including retinoid derivatives have a potential therapeutic utility for treatment of HTLV-1(+) T cell leukemia without any effect on HTLV-I(-) cells.

Cell Cycle↗
PubMed1994

Neuroprotection by glial cells through adult T cell leukemia-derived factor/human thioredoxin (ADF/TRX).

Adult T cell leukemia-derived factor (ADF) is a human homologue of thioredoxin (TRX) with many biological functions and is induced by various stimuli and stress. In the central nervous system (CNS), expression of ADF/TRX occurs in glial cells during ischemia and reperfusion. We showed that ADF/TRX was actively released from U251 astrocytoma cells upon exposure to a low concentration of H2O2. The addition of conditioned medium from H2O2-stimulated U251 cells or recombinant ADF (rADF) to the culture medium promoted the survival of neurons from embryonic mouse cortex and striatum, but the addition of mutant ADF (mADF), which has no reducing activity, did not. In addition to rADF, incubation with two other thiol compounds, 2-mercaptoethanol (2-ME) and N-acetyl-L-cysteine (NAC), also increased the neuronal cell survival rate. In contrast, L-buthionine-(S,R)-sulfoximine (BSO), which inhibited the synthesis of glutathione (GSH), decreased the neuronal cell survival rate. Intracellular GSH was increased by incubation with rADF for 24 h, as it is with 2-ME and NAC. Redox active molecules such as thiol compounds may be survival factors for central neurons in vitro, and this capacity may be supplied by endogenous molecules, such as ADF/TRX and glutathione, under certain pathologic conditions in vivo.

Acetylcysteine↗
PubMed1994

Thiol-mediated redox regulation of lymphocyte proliferation. Possible involvement of adult T cell leukemia-derived factor and glutathione in transferrin receptor expression.

The proliferative response of PBMC to PHA, Con A, OKT3 mAb and IL-2-dependent proliferation of PHA-blasts was examined in a thiol-free environment (cultured in a L-cystine- and GSH-free medium). [3H]TdR incorporation assay and cell cycle analysis revealed that stimulated PBMC could not enter the S phase when deprived of these thiol compounds. In thiol-free cultures, an increase in intracellular free Ca2+ concentration and IL-2R alpha-chain/p 55 (Tac) induction was still observed, whereas transferrin receptor induction was markedly reduced, suggesting that the proliferative response of mitogenically stimulated PBMC was arrested in the late G1 phase in which transferrin receptor is induced. In GSH-depleted cultures, a similar reduction of the proliferative response of PBMC and PHA-blasts was observed when the concentration of L-cystine was lowered, in a dose-dependent manner. Each reduction or loss of proliferative response was partially restored by supplementation of 2-ME or adult T cell leukemia-derived factor (ADF)/human thioredoxin which is considered to be an endogenous dithiol-reducing factor. L-Cystine transport analysis showed that mitogenically stimulated PBMC and PHA blasts incorporated L-cystine, whereas resting PBMC did not. Furthermore, ADF as well as 2-ME exhibited an enhancing activity on the L-cystine transport in PHA blasts. Together with the fact that L-cystine transport is a limiting step in glutathione synthesis, these findings suggest that GSH and ADF might cooperate in the thiol-mediated redox regulation process and might also play key roles in cell cycle (late G1 to S) progression of activated lymphocytes.

Amino Acid Sequence↗
PubMed1994

Mouse thioredoxin gene maps on chromosome 4, whereas its pseudogene maps on chromosome 1.

Thioredoxins are involved in various biochemical systems and mediate both redox and nonredox functions. In mammalian cells, thioredoxin functions as an endogenous glucocorticoid receptor activating factor and as an adult T-cell leukemia-derived factor (ADF) that stimulates expression of interleukin-2 receptor in human T-cell leukemia virus (HTLV)-I transformed T cells. We have mapped the thioredoxin gene (Txn) and its processed pseudogene (Txn-ps1) in the mouse using a panel of interspecific backcross mice. Txn maps to Chr 4, whereas Txn-ps1 maps to the proximal region of Chr 1.

Animals↗
PubMed1994

Soluble Fc epsilon RII/CD23 in patients with autoimmune diseases and Epstein-Barr virus-related disorders: analysis by ELISA for soluble Fc epsilon RII/CD23.

The low-affinity Fc receptor for IgE (Fc epsilon RII/CD23) and its soluble form (sCD23, IgE-binding factor) have multiple functions, and enhanced levels of these are associated with various immunological diseases. We established two sensitive ELISA systems using enzyme-conjugated mAb and biotinylated mAb. The detection limits of the ELISA systems were 0.03 and 1.0 ng/ml, which showed good correlation in the range 1.0-10 ng/ml. In the ELISA system using enzyme-conjugated mAb, the average sCD23 concentration in 303 normal healthy volunteers was 1.4 +/- 0.3 ng/ml. In the ELISA system using biotinylated mAb, sCD23 levels in normal healthy volunteers showed almost the same values. In patients with autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, progressive systemic sclerosis, and mixed connective tissue disease, the sCD23 levels were significantly higher than those in normal individuals. Furthermore, in Epstein-Barr virus-related disorders after liver transplantation with immunosuppression, plasma levels of sCD23 rapidly increased to more than 12 ng/ml when clinical symptoms were evident. In addition, the sCD23 values remained high, although elevated GOT levels gradually decreased to standard values and EBV hepatitis improved. These data suggest that sCD23 levels are a sensitive marker of autoimmune diseases and EBV-related disorders in addition to allergic disorders. The ELISA system for sCD23 may be an additional diagnostic tool in estimating the clinical courses of these diseases.

Adult↗
PubMed1994

Adult T cell leukemia-derived factor/human thioredoxin protects endothelial F-2 cell injury caused by activated neutrophils or hydrogen peroxide.

Adult T cell leukemia-derived factor (ADF), originally defined as an interleukin 2 receptor/alpha (alpha) chain inducer produced by human T-lymphotropic virus type-I transformed cells, is identical to human thioredoxin (TRX). In this study, the protective effect of ADF/TRX on the cytotoxicity of endothelial cells caused by phorbol myristate acetate (PMA)-activated neutrophils or hydrogen peroxide (H2O2) was examined. When murine endothelial F-2 cells established from an ultraviolet light-induced tumor on a nude mouse were incubated with PMA-activated neutrophils or with 1 mM H2O2 for 6 hours, the cytotoxicity of F-2 cells was respectively 51 +/- 4% or 40 +/- 8% by the 51Cr releasing assay. Recombinant ADF/TRX (rADF/TRX) inhibited this cytotoxicity in a dose-dependent manner, although mutant ADF/TRX (cysteine 31 to serine), 2-mercaptoethanol and dithiothreitol did not. On a molar basis, rADF/TRX was more effective than glutathione but less effective than catalase. Immunoblotting analysis showed that treatment with 0.1 mM H2O2 induced murine TRX on F-2 cells. These findings indicate that ADF/TRX is an oxidative stress-inducible endogenous protein and rADF/TRX plays a protective role against activated neutrophils- or H2O2-induced endothelial cytotoxicity.

Animals↗
PubMed1994

Detection of adult T-cell leukemia-derived factor/human thioredoxin in human serum.

Adult T-cell leukemia (ATL)-derived factor (ADF), originally defined as an inducer of interleukin-2 receptor/alpha-chain (IL-2R/p55) of human T-lymphotropic virus type I (HTLV-I) positive T cells, is a human homologue of redox-active coenzyme thioredoxin (Trx) of Escherichia coli. In this study, an enzymatic assay system based on the dithiol-dependent insulin-reducing activity of ADF/Trx was established (insulin-reducing assay) to determine the amount of ADF/Trx in human serum using NADPH and Trx reductase purified from human placenta. Insulin-reducing activity was detected in all of the serum samples from healthy volunteers (n = 30) screened by this assay, with a mean +/- SD of 10.9 +/- 2.4 U/l. This mean value corresponds with the concentration of 223 ng recombinant ADF/Trx (rADF/Trx)/ml. Human serum is known to contain several redox-active proteins with ADF/Trx motifs. To differentiate the contribution of these proteins and ADF/Trx to the insulin-reducing activity, the anti-rADF/Trx monoclonal antibody (mAb)-conjugated affinity column-depleted sera obtained from an identical source was used for analysis. The affinity column-depleted sera demonstrated a loss of over 99% of the original activity, while control column depleted sera lost less than 4%. Furthermore, the amount of affinity-purified ADF/Trx molecules eluted from the same column almost corresponded with the amount estimated by the insulin-reducing activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Measurement of ADF/thioredoxin in human serum and its clinical significance].

The adult T cell leukemia (ATL)-derived factor (ADF) was first described as an interleukin 2 receptor alpha chain (IL-2R alpha) inducing factor which is produced by an HTLV-I infected cell line. Subsequent purification and gene cloning proved that it is a human homologue of a bacterial reducing coenzyme, thioredoxin (TRX). ADF/human TRX (hTRX) has multiple functions both in the extracellular and intracellular compartments, such as cytokine activity, dithiol-reducing activity and radical scavenging activity. ADF/hTRX can facilitate the interactions between the transcriptional factors and its target DNA sequences, which may result in the overexpression of IL -2R alpha in HTLV-I infected cells. Recently, we have detected the presence of ADF/hTRX in human serum (sADF) obtained from healthy volunteers using the insulin reducing assay and Western blotting analysis. Another endogenous redox regulator, glutathione (GSH) system, has long been studied for its relation to cell proliferation and activation. Our recent data showed that thiol compounds such as L-cysteine and GSH may be involved in the activation and cell cycle progression of stimulated lymphocytes. We have also found that ADF/hTRX promotes L-cysteine transport into the cells and increases intracellular GSH content, indicating the close association between ADF/hTRX and GSH systems. Redox regulation by ADF/hTRX and GSH systems seems to play an important role in regulating cell proliferation and activation. To assess the possible alteration of the sADF level in pathological conditions, such as viral infections, an ELISA system for ADF/hTRX was recently established using two different monoclonal antibodies against rADF.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytokines↗
PubMed1994

Oxidative stress induces adult T cell leukemia derived factor/thioredoxin in the rat retina.

BACKGROUND: Adult T cell leukemia derived factor (ADF), originally defined as an interleukin-2 receptor inducer, is a human thioredoxin homolog. ADF/thioredoxin has several biologic functions, such as defense against cellular damage, activity to scavenge oxidative stress by hydrogen peroxide radicals and cytokine-like properties. We hypothesized that under certain conditions, ischemia followed by reperfusion and/or light exposure, ADF may be induced in the retina. EXPERIMENTAL DESIGN: To test this hypothesis, we prepared experimental animal models in which oxidative stress could be applied to the retina. In the present study, we examined ADF expression in the rat retina using temporary ischemia and reperfusion, and photodynamic retinal vascular thrombosis by immunohistochemical and Western blotting methods. RESULTS: ADF expression was strongly induced in the retinal pigment epithelial cells after 2 hours of ischemia followed by 2, 24, or 48 hours of reperfusion. ADF was also expressed in retinal pigment epithelial cells as early as 3 hours after light exposure followed by rose bengal injection, and this expression increased with time. Western blotting data showed that ADF expression increased in the retinal pigment epithelial cells in the experimental group, as compared with the control group. These results indicate that ADF is actively induced in retinal pigment epithelial cells upon oxidative stress. CONCLUSIONS: ADF induction in retinal pigment epithelial cells may be involved in the defense mechanism against cellular damage caused by active oxygen species generated during oxygen stress to the retina.

Animals↗
PubMed1994

Mitochondrial induction of adult T cell leukemia derived factor (ADF/hTx) after oxidative stresses in retinal pigment epithelial cells.

PURPOSE: Adult T cell leukemia derived factor (ADF) is a human homologue of thioredoxin (hTx), which exhibits scavenging activity with reactive oxygen intermediates. In their previous study, the authors found that after transient retinal ischemia, the expression of thioredoxin in rat retinal pigment epithelium (RPE) layer increased markedly. The present investigation is to determine intracellular ADF localization in RPE after transient ischemia and in cultured human RPE cells after oxidative insult by H2O2. METHODS: The authors employed immunoelectron microscopy to examine ADF localization in RPE. Labeling density analysis was performed to supplement the main observation in the experiment of transient retinal ischemia. 3-(4,5-dimethylthiazol-2yl)-2-5-diphenyltetrazolium bromide (MTT) assay was performed to verify the protective role of recombinant ADF (rADF) against H2O2. RESULTS: In immunogold electron microscopy, sparse ADF-positive labeling was seen in the cytosol and mitochondria in normal rat RPE and in untreated cultured RPE cells. After oxidative stress, it was concentrated in mitochondria in both groups. MTT assay proved that rADF protected cultured RPE from the toxicity of H2O2. CONCLUSIONS: This study shows the induction of ADF/hTx in mitochondria of RPE after oxidative stresses and its protective effect on cultured RPE exposed to H2O2. The data indicate the possibly important role of ADF/hTx in the protection of retinal cells from the oxidative stresses associated with retinal ischemic disease and probably with regular visual activity.

Adult↗
PubMed1993

Effects of 2-mercaptoethanol on survival and differentiation of fetal mouse brain neurons cultured in vitro.

Effects of 2-mercaptoethanol on primary cultures of fetal mouse brain neurons have been investigated. The addition of 2-mercaptoethanol to the culture medium increased 6- or 200-fold the survival rates of embryonic day-16 murine striatum neurons and day-18 cerebral cortical neurons cultured in serum-free medium, respectively, and also induced neurite outgrowth, particularly being prominent in cortical neurons. Moreover, this drug enhanced trophic activities of the conditioned medium of VR-2g or BIM cells. These findings indicate that 2-mercaptoethanol can support the viability and differentiation of fetal mouse brain neurons.

Animals↗