Human thioredoxin (TRX) is a 12-kDa protein with redox-active dithiol in the active site -Cys-Gly... more Human thioredoxin (TRX) is a 12-kDa protein with redox-active dithiol in the active site -Cys-Gly-Pro-Cys-, which is induced by biological stress due to oxidative damage, metabolic dysfunction, chemicals, infection/inflammation, irradiation, or hypoxia/ischemia-reperfusion. Our research has demonstrated that exogenous TRX is effective in a wide variety of inflammatory diseases, including viral pneumonia, acute lung injury, gastric injury, and dermatitis, as well as in the prevention and amelioration of food allergies. Preclinical and clinical studies using recombinant TRX (rhTRX) are now underway. We have also identified substances that induce the expression of TRX in the body, in vegetables and other plant ingredients. Skincare products are being developed that take advantage of the anti-inflammatory and anti-allergic action of TRX. Furthermore, we are currently engaged in the highly efficient production of pure rhTRX in several plants, such as lettuce, grain and rice.
It is important throughout the life of animals to regulate the oxygen concentration and to scaven... more It is important throughout the life of animals to regulate the oxygen concentration and to scavenge oxygen radicals. Reactive oxygen species (ROS) are generated as by-products in the respiratory system and are increased under inflammatory conditions. Oxidative stress is induced by ROS production which exceeds the cell's ability to detoxify ROS and is involved in many diseases, such as heart failure, Alzheimer's disease, Parkinson's disease and cancer. Among the key antioxidant enzymes, thioredoxin and glutaredoxin play important roles in cell defense against oxidative stress and the maintenance of redox homeostasis. Thioredoxin is a small redox active protein distributed ubiquitously in various mammalian tissues and cells and acts not only as an antioxidant but also an anti-inflammatory and an antiapoptotic protein. Here we discuss the roles of thioredoxin on oxygen stress and redox regulation.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Thioredoxin binding protein-2 (TBP-2), which is identical with vitamin D3 (VD3) up-regulated prot... more Thioredoxin binding protein-2 (TBP-2), which is identical with vitamin D3 (VD3) up-regulated protein 1 (VDUP1), plays a crucial role in the integration of glucose and lipid metabolism. There are three highly homologous genes of TBP-2/vitamin D3 up-regulated protein 1 in humans, but their functions remain unclear. Here we characterized a TBP-2 homolog, TBP-2-like inducible membrane protein (TLIMP). In contrast to TBP-2, TLIMP displayed no significant binding affinity for thioredoxin. TLIMP exhibited an inner membrane-associated pattern of distribution and also colocalized with transferrin and low-density lipoprotein, indicating endosome-and lyso-some-associated functions. VD3 and ligands of peroxisome proliferator-activated receptor (PPAR)-␥, an important regulator of energy metabolism and cell growth inhibition, induced the expression of TLIMP as well as TBP-2. Overexpression of TLIMP suppressed both anchorage-dependent and-independent cell growth and PPAR␥ ligand-inducible gene activation. These results suggest that TLIMP, a novel VD3-or PPAR␥ ligand-inducible membrane-associated protein, plays a regulatory role in cell proliferation and PPAR␥ activation.
In the above paper, the last author's middle initial was given incorrectly. It is correct as give... more In the above paper, the last author's middle initial was given incorrectly. It is correct as given above.
To evaluate the effect of a nano-spray instrument, we examined the transcutaneous permeability of... more To evaluate the effect of a nano-spray instrument, we examined the transcutaneous permeability of human recombinant thioredoxin (rhTRX) and human recombinant epidermal growth factor (rhEGF). Distribution of rhTRX and rhEGF in skin tissues was studied by immunohistochemical analyses after their application. At least 1 μg/ml rhEGF was distributed in the epidermis after application using the nano-spray instrument. Permeability of rhEGF decreased if the spraying time was shorter or the spraying distance was longer. Sprayed rhTRX was distributed more densely in the epidermis, and could strongly suppressed irritant contact dermatitis induced by croton oil, compared with the painted rhTRX group. These data suggest that aerosol delivery is a safe and effective method of enhancement of drug permeation into skin, and could be used to improve the effects of drugs.
The present study was performed to assess the protective role of thioredoxin/adult T-cell leukemi... more The present study was performed to assess the protective role of thioredoxin/adult T-cell leukemia-derived factor (TRX/ADF) on the liver and brain cell damages induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in ADF wild-type (WT) and transgenic (Tg) mice. The ADF WT and Tg mice were intraperitoneally injected with a single dose of TCDD (150 µg/kg body weight). One day after the treatment, the liver and brain tissues were examined electron microscopically to evaluate the cellular toxicity. In the ADF WT mice, marked reduction of subcellular components, such as mitochondria, rough endoplasmic reticula, and glycogen granules, as well as swelling of the remaining mitochondria, were evident in the liver cells. However, attenuation of these changes was evident in TCDD-treated TRX/ ADF mice. Similar subcellular changes noted in the neuronal cells of TCDD-treated WT mice were also attenuated in Tg mice. The results suggest that oxidative cellular damage contributes to the acute toxicity induced by TCDD and that TRX/ADF protects against it.
A continuous cell line (YT cells) with inducible receptor for T cell growth factor (TCGF)/interle... more A continuous cell line (YT cells) with inducible receptor for T cell growth factor (TCGF)/interleukin 2 (IL 2) was established from a 15-yr-old boy with acute lymphoblastic lymphoma and thymoma. YT cells were tetraploid, having 4q+ chromosomal markers, and proliferated continuously in vitro without conditioned medium (CM) or IL 2. They were weakly positive for OKT9, OKT11, and Tac antigen (Ag), a determinant closely associated with the receptor for IL 2 (IL 2-R), and were negative for OKT1, OKT3, OKT4, and OKT8 Ag. YT cells also expressed HNK-1 Ag and Fc receptors for IgG, which are expressed on natural killer (NK) cells. They retained a killing activity against human cell lines, including K562 (myeloid), T, and B cell lines. Unlike Tac Ag/IL 2-R(+) cell lines derived from adult T cell leukemia (ATL), YT cells were negative for HTLV, as proved by Southern blotting with cDNA for viral DNA. The expression of Tac Ag was markedly enhanced in 18 hr, when YT cells were incubated with CM f...
Protective activity of adult T cell leukemia-derived factor (ADF) against tumor necrosis factor-d... more Protective activity of adult T cell leukemia-derived factor (ADF) against tumor necrosis factor-dependent cytotoxicity on U937 cells.
Chronic obstructive pulmonary disease (COPD) is emphysema and/or chronic bronchitis characterised... more Chronic obstructive pulmonary disease (COPD) is emphysema and/or chronic bronchitis characterised by long-term breathing problems and poor airflow. The prevalence of COPD has increased over the last decade and the drugs most commonly used to treat it, such as glucocorticoids and bronchodilators, have significant therapeutic effects; however, they also cause side effects, including infection and immunosuppression. Here we reviewed the pathogenesis and progression of COPD and elaborated on the effects and mechanisms of newly developed molecular targeted COPD therapeutic drugs. Among these new drugs, we focussed on thioredoxin (Trx). Trx effectively prevents the progression of COPD by regulating redox status and protease/anti-protease balance, blocking the NF-κB and MAPK signalling pathways, suppressing the activation and migration of inflammatory cells and the production of cytokines, inhibiting the synthesis and the activation of adhesion factors and growth factors, and controlling t...
SIGNIFICANCE The pathogenesis and progression of allergic inflammation in the respiratory system ... more SIGNIFICANCE The pathogenesis and progression of allergic inflammation in the respiratory system are closely linked to oxidative stress. Thioredoxin (TRX) is an essential redox balance regulator in organisms and is induced by various oxidative stress factors, including ultraviolet rays, radiation, oxidation, viral infections, ischemia reperfusion, and anticancer agents. Recent Advances: We demonstrated that systemic administration and transgenic overexpression of TRX is useful in a wide variety of in vivo inflammatory respiratory diseases models, such as viral pneumonia, interstitial lung disease, chronic obstructive pulmonary disease, asthma, acute respiratory distress syndrome, and obstructive sleep apnea syndrome, by removing reactive oxygen species (ROS), blocking production of inflammatory cytokines, inhibiting migration and activation of neutrophils and eosinophils, and regulating the cellular redox status. In addition, TRX's anti-inflammatory mechanism is different from the mechanisms associated with anti-inflammatory agents, such as glucocorticoids, which regulate the inflammatory reaction in association with suppressing immune responses. CRITICAL ISSUES Understanding the molecular mechanism of TRX is very helpful for understanding the role of TRX in respiratory diseases. In this review, we show the protective effect of TRX in various respiratory diseases. In addition, we discuss its anti-allergic and anti-inflammatory molecular mechanism in detail. FUTURE DIRECTIONS The application of TRX may be useful for treating respiratory allergic inflammatory disorders.
Nihon rinsho. Japanese journal of clinical medicine, 1996
Fc epsilon R II/CD23 is a low affinity Fc receptor for IgE. It plays various biological roles. In... more Fc epsilon R II/CD23 is a low affinity Fc receptor for IgE. It plays various biological roles. In this paper, we reviewed recent knowledge of this molecule.
Cells expressing Fc receptors for IgE (Fc epsilon RII) were identified in the peripheral blood fr... more Cells expressing Fc receptors for IgE (Fc epsilon RII) were identified in the peripheral blood from patients with atopic dermatitis and with eczematous dermatitis, and normal non-atopic subjects by using monoclonal antibodies to human lymphocyte Fc epsilon RII, and to lymphoid cell-surface antigens by immunofluorescence staining. Based on the extent of the dermatitis patients were classified as severe (greater than 50% skin surface involved), moderate (50-10%) and mild (less than 10%). Patients with severe and moderate atopic dermatitis had 5.9% and 5.7% Fc epsilon RII+ peripheral blood mononuclear cells (PBMC), respectively, that were significantly higher than percentages in mild atopic dermatitis patients (2.6%), severe to moderate eczematous dermatitis patients (2.3%), mild eczematous dermatitis patients (2.2%) and normal individuals (1.7%)(0.05 greater than P). In severe and moderate atopic dermatitis patients, 10% of Fc epsilon RII+ PBMC were T cells that preferentially express...
Human thioredoxin (TRX) is a 12-kDa protein with redox-active dithiol in the active site -Cys-Gly... more Human thioredoxin (TRX) is a 12-kDa protein with redox-active dithiol in the active site -Cys-Gly-Pro-Cys-, which is induced by biological stress due to oxidative damage, metabolic dysfunction, chemicals, infection/inflammation, irradiation, or hypoxia/ischemia-reperfusion. Our research has demonstrated that exogenous TRX is effective in a wide variety of inflammatory diseases, including viral pneumonia, acute lung injury, gastric injury, and dermatitis, as well as in the prevention and amelioration of food allergies. Preclinical and clinical studies using recombinant TRX (rhTRX) are now underway. We have also identified substances that induce the expression of TRX in the body, in vegetables and other plant ingredients. Skincare products are being developed that take advantage of the anti-inflammatory and anti-allergic action of TRX. Furthermore, we are currently engaged in the highly efficient production of pure rhTRX in several plants, such as lettuce, grain and rice.
It is important throughout the life of animals to regulate the oxygen concentration and to scaven... more It is important throughout the life of animals to regulate the oxygen concentration and to scavenge oxygen radicals. Reactive oxygen species (ROS) are generated as by-products in the respiratory system and are increased under inflammatory conditions. Oxidative stress is induced by ROS production which exceeds the cell's ability to detoxify ROS and is involved in many diseases, such as heart failure, Alzheimer's disease, Parkinson's disease and cancer. Among the key antioxidant enzymes, thioredoxin and glutaredoxin play important roles in cell defense against oxidative stress and the maintenance of redox homeostasis. Thioredoxin is a small redox active protein distributed ubiquitously in various mammalian tissues and cells and acts not only as an antioxidant but also an anti-inflammatory and an antiapoptotic protein. Here we discuss the roles of thioredoxin on oxygen stress and redox regulation.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Thioredoxin binding protein-2 (TBP-2), which is identical with vitamin D3 (VD3) up-regulated prot... more Thioredoxin binding protein-2 (TBP-2), which is identical with vitamin D3 (VD3) up-regulated protein 1 (VDUP1), plays a crucial role in the integration of glucose and lipid metabolism. There are three highly homologous genes of TBP-2/vitamin D3 up-regulated protein 1 in humans, but their functions remain unclear. Here we characterized a TBP-2 homolog, TBP-2-like inducible membrane protein (TLIMP). In contrast to TBP-2, TLIMP displayed no significant binding affinity for thioredoxin. TLIMP exhibited an inner membrane-associated pattern of distribution and also colocalized with transferrin and low-density lipoprotein, indicating endosome-and lyso-some-associated functions. VD3 and ligands of peroxisome proliferator-activated receptor (PPAR)-␥, an important regulator of energy metabolism and cell growth inhibition, induced the expression of TLIMP as well as TBP-2. Overexpression of TLIMP suppressed both anchorage-dependent and-independent cell growth and PPAR␥ ligand-inducible gene activation. These results suggest that TLIMP, a novel VD3-or PPAR␥ ligand-inducible membrane-associated protein, plays a regulatory role in cell proliferation and PPAR␥ activation.
In the above paper, the last author's middle initial was given incorrectly. It is correct as give... more In the above paper, the last author's middle initial was given incorrectly. It is correct as given above.
To evaluate the effect of a nano-spray instrument, we examined the transcutaneous permeability of... more To evaluate the effect of a nano-spray instrument, we examined the transcutaneous permeability of human recombinant thioredoxin (rhTRX) and human recombinant epidermal growth factor (rhEGF). Distribution of rhTRX and rhEGF in skin tissues was studied by immunohistochemical analyses after their application. At least 1 μg/ml rhEGF was distributed in the epidermis after application using the nano-spray instrument. Permeability of rhEGF decreased if the spraying time was shorter or the spraying distance was longer. Sprayed rhTRX was distributed more densely in the epidermis, and could strongly suppressed irritant contact dermatitis induced by croton oil, compared with the painted rhTRX group. These data suggest that aerosol delivery is a safe and effective method of enhancement of drug permeation into skin, and could be used to improve the effects of drugs.
The present study was performed to assess the protective role of thioredoxin/adult T-cell leukemi... more The present study was performed to assess the protective role of thioredoxin/adult T-cell leukemia-derived factor (TRX/ADF) on the liver and brain cell damages induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in ADF wild-type (WT) and transgenic (Tg) mice. The ADF WT and Tg mice were intraperitoneally injected with a single dose of TCDD (150 µg/kg body weight). One day after the treatment, the liver and brain tissues were examined electron microscopically to evaluate the cellular toxicity. In the ADF WT mice, marked reduction of subcellular components, such as mitochondria, rough endoplasmic reticula, and glycogen granules, as well as swelling of the remaining mitochondria, were evident in the liver cells. However, attenuation of these changes was evident in TCDD-treated TRX/ ADF mice. Similar subcellular changes noted in the neuronal cells of TCDD-treated WT mice were also attenuated in Tg mice. The results suggest that oxidative cellular damage contributes to the acute toxicity induced by TCDD and that TRX/ADF protects against it.
A continuous cell line (YT cells) with inducible receptor for T cell growth factor (TCGF)/interle... more A continuous cell line (YT cells) with inducible receptor for T cell growth factor (TCGF)/interleukin 2 (IL 2) was established from a 15-yr-old boy with acute lymphoblastic lymphoma and thymoma. YT cells were tetraploid, having 4q+ chromosomal markers, and proliferated continuously in vitro without conditioned medium (CM) or IL 2. They were weakly positive for OKT9, OKT11, and Tac antigen (Ag), a determinant closely associated with the receptor for IL 2 (IL 2-R), and were negative for OKT1, OKT3, OKT4, and OKT8 Ag. YT cells also expressed HNK-1 Ag and Fc receptors for IgG, which are expressed on natural killer (NK) cells. They retained a killing activity against human cell lines, including K562 (myeloid), T, and B cell lines. Unlike Tac Ag/IL 2-R(+) cell lines derived from adult T cell leukemia (ATL), YT cells were negative for HTLV, as proved by Southern blotting with cDNA for viral DNA. The expression of Tac Ag was markedly enhanced in 18 hr, when YT cells were incubated with CM f...
Protective activity of adult T cell leukemia-derived factor (ADF) against tumor necrosis factor-d... more Protective activity of adult T cell leukemia-derived factor (ADF) against tumor necrosis factor-dependent cytotoxicity on U937 cells.
Chronic obstructive pulmonary disease (COPD) is emphysema and/or chronic bronchitis characterised... more Chronic obstructive pulmonary disease (COPD) is emphysema and/or chronic bronchitis characterised by long-term breathing problems and poor airflow. The prevalence of COPD has increased over the last decade and the drugs most commonly used to treat it, such as glucocorticoids and bronchodilators, have significant therapeutic effects; however, they also cause side effects, including infection and immunosuppression. Here we reviewed the pathogenesis and progression of COPD and elaborated on the effects and mechanisms of newly developed molecular targeted COPD therapeutic drugs. Among these new drugs, we focussed on thioredoxin (Trx). Trx effectively prevents the progression of COPD by regulating redox status and protease/anti-protease balance, blocking the NF-κB and MAPK signalling pathways, suppressing the activation and migration of inflammatory cells and the production of cytokines, inhibiting the synthesis and the activation of adhesion factors and growth factors, and controlling t...
SIGNIFICANCE The pathogenesis and progression of allergic inflammation in the respiratory system ... more SIGNIFICANCE The pathogenesis and progression of allergic inflammation in the respiratory system are closely linked to oxidative stress. Thioredoxin (TRX) is an essential redox balance regulator in organisms and is induced by various oxidative stress factors, including ultraviolet rays, radiation, oxidation, viral infections, ischemia reperfusion, and anticancer agents. Recent Advances: We demonstrated that systemic administration and transgenic overexpression of TRX is useful in a wide variety of in vivo inflammatory respiratory diseases models, such as viral pneumonia, interstitial lung disease, chronic obstructive pulmonary disease, asthma, acute respiratory distress syndrome, and obstructive sleep apnea syndrome, by removing reactive oxygen species (ROS), blocking production of inflammatory cytokines, inhibiting migration and activation of neutrophils and eosinophils, and regulating the cellular redox status. In addition, TRX's anti-inflammatory mechanism is different from the mechanisms associated with anti-inflammatory agents, such as glucocorticoids, which regulate the inflammatory reaction in association with suppressing immune responses. CRITICAL ISSUES Understanding the molecular mechanism of TRX is very helpful for understanding the role of TRX in respiratory diseases. In this review, we show the protective effect of TRX in various respiratory diseases. In addition, we discuss its anti-allergic and anti-inflammatory molecular mechanism in detail. FUTURE DIRECTIONS The application of TRX may be useful for treating respiratory allergic inflammatory disorders.
Nihon rinsho. Japanese journal of clinical medicine, 1996
Fc epsilon R II/CD23 is a low affinity Fc receptor for IgE. It plays various biological roles. In... more Fc epsilon R II/CD23 is a low affinity Fc receptor for IgE. It plays various biological roles. In this paper, we reviewed recent knowledge of this molecule.
Cells expressing Fc receptors for IgE (Fc epsilon RII) were identified in the peripheral blood fr... more Cells expressing Fc receptors for IgE (Fc epsilon RII) were identified in the peripheral blood from patients with atopic dermatitis and with eczematous dermatitis, and normal non-atopic subjects by using monoclonal antibodies to human lymphocyte Fc epsilon RII, and to lymphoid cell-surface antigens by immunofluorescence staining. Based on the extent of the dermatitis patients were classified as severe (greater than 50% skin surface involved), moderate (50-10%) and mild (less than 10%). Patients with severe and moderate atopic dermatitis had 5.9% and 5.7% Fc epsilon RII+ peripheral blood mononuclear cells (PBMC), respectively, that were significantly higher than percentages in mild atopic dermatitis patients (2.6%), severe to moderate eczematous dermatitis patients (2.3%), mild eczematous dermatitis patients (2.2%) and normal individuals (1.7%)(0.05 greater than P). In severe and moderate atopic dermatitis patients, 10% of Fc epsilon RII+ PBMC were T cells that preferentially express...
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