Isao Nagaoka - Academia.edu (original) (raw)

Papers by Isao Nagaoka

Research paper thumbnail of Activated peritoneal macrophages inhibit the proliferation of rat ascites hepatoma AH-130 cells via the production of tumor necrosis factor- α and nitric oxide

Inflammation Research, Oct 1, 2000

To study the effect of peritoneal macrophages on tumor cell proliferation, we cultured ascites he... more To study the effect of peritoneal macrophages on tumor cell proliferation, we cultured ascites hepatoma AH-130 cells with unstimulated, or lipopolysaccharide (LPS)- or interleukin (IL)-2-stimulated rat peritoneal macrophages, and examined the proliferation of AH-130 cells. Rat peritoneal macrophages isolated from male Wistar rats were co-cultured with AH-130 cells in the absence or presence of LPS or IL-2. After incubation, proliferation of AH-130 cells was analyzed using flow cytometry. In addition, the levels of tumor necrosis factor (TNF)-alpha and nitric oxide (NOx, nitrate + nitrite) in the culture supernatants were measured. Furthermore, anti-TNF-alpha antibody (10 microg/ml) and nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA, 100 microM) were added to the coculture, and their effect on AH-130 cell proliferation was examined. When AH-130 cells were co-cultured with unstimulated peritoneal macrophages, proliferation of AH-130 cells was not affected. In contrast, when AH-130 cells were cocultured with peritoneal macrophages in the presence of LPS (0.1-20 microg/ml) or IL-2 (1-200 U/ml), proliferation of AH130 cells was dose-dependently suppressed by LPS or IL-2. Moreover, LPS- or IL-2-stimulation increased the levels of TNF-alpha and NOx in the supernatants of AH-130 cell and macrophage co-culture, although LPS and IL-2 did not induce TNF-alpha and NOx production by AH-130 cells incubated without macrophages. Interestingly, anti-TNF-alpha antibody and L-NMMA significantly inhibited the suppression of AH-130 cell proliferation by LPS- or IL-2-stimulated macrophages (p < 0.05). Furthermore, exogenously added recombinant rat TNF-alpha (0.26-1300 ng/ml) or NO donor (GSNO, S-nitroso-L-glutathione) (0.1 - 10 mM) dose-dependently suppressed the proliferation of AH-130 cells in the absence of macrophages. Together these observations suggest that when peritoneal macrophages are activated by LPS and IL-2, they suppress the proliferation of ascites hepatoma AH-130 cells via the production of TNF-alpha and nitric oxide.

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Research paper thumbnail of Phytochemicals and Vitamin D for a Healthy Life and Prevention of Diseases

International Journal of Molecular Sciences

A variety of phytocompounds contained in medical plants have been used as medication, including K... more A variety of phytocompounds contained in medical plants have been used as medication, including Kampo (traditional Japanese) medicine. Phytochemicals are one category of the chemical compounds mainly known as antioxidants, and recently, their anti-inflammatory effects in preventing chronic inflammation have received much attention. Here, we present a narrative review of the health-promotion and disease-prevention effects of phytochemicals, including polyphenols, the latter of which are abundant in onions, oranges, tea, soybeans, turmeric, cacao, and grapes, along with the synergetic effects of vitamin D. A phenomenon currently gaining popularity in Japan is finding non-disease conditions, so-called ME-BYO (mibyou) and treating them before they develop into illnesses. In addition to lifestyle-related diseases such as metabolic syndrome and obesity, dementia and frailty, commonly found in the elderly, are included as underlying conditions. These conditions are typically induced by chr...

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Research paper thumbnail of Consumption of yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 augments serum antibody titers against seasonal influenza vaccine in healthy adults

Bioscience of Microbiota, Food and Health

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Research paper thumbnail of Lipopolysaccharides and Cellular Senescence: Involvement in Atherosclerosis

International Journal of Molecular Sciences

Atherosclerosis is a chronic inflammatory disease of the vascular walls related to aging. Thus fa... more Atherosclerosis is a chronic inflammatory disease of the vascular walls related to aging. Thus far, the roles of cellular senescence and bacterial infection in the pathogenesis of atherosclerosis have been speculated to be independent of each other. Some types of macrophages, vascular endothelial cells, and vascular smooth muscle cells are in a senescent state at the sites of atherosclerotic lesions. Likewise, bacterial infections and accumulations of lipopolysaccharide (LPS), an outer-membrane component of Gram-negative bacteria, have also been observed in the atherosclerotic lesions of patients. This review introduces the integration of these two potential pathways in atherosclerosis. Previous studies have suggested that LPS directly induces cellular senescence in cultured monocytes/macrophages and vascular cells. In addition, LPS enhances the inflammatory properties (senescence-associated secretory phenotype [SASP]) of senescent endothelial cells. Thus, LPS derived from Gram-nega...

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Research paper thumbnail of Evaluation of the effect of administering N-acetyl-glucosamine-containing green tea supplement on biomarkers for cartilage metabolism in healthy individuals without symptoms of arthritis: a randomized double-blind placebo-controlled clinical study

Functional Foods in Health and Disease, 2016

Background: To evaluate the chondroprotective action of an N-acetyl-glucosamine (GlcNAc)-containi... more Background: To evaluate the chondroprotective action of an N-acetyl-glucosamine (GlcNAc)-containing supplement on the joint health of healthy individuals without symptoms of arthritis, we conducted a randomized double-blind placebo-controlled clinical trial. Methods: Subjects (n=100, 51.3 ± 1.0 years (mean ± SE)) without symptoms of arthritis were randomly assigned to receive a 1000 mg GlcNAc-containing diet (GlcNAc group) or a placebo diet (placebo group) once a day for 16 weeks, and the effect on the cartilage metabolism was evaluated by analyzing the ratio of type II collagen degradation to synthesis using type II collagen degradation (C2C) and synthesis (PIICP) markers.Results: The results indicated that the changes in the C2C/PIICP ratios from the baseline were slightly suppressed in the GlcNAc group compared with those in the placebo group at weeks 16 during the intervention and 4 weeks after the intervention. However, there was no significant difference between the two groups...

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Research paper thumbnail of Platelet-derived growth factor-A and -B gene expression during maturation of monocytes to macrophages

Ensho, 1993

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Research paper thumbnail of Studies on the leukotriene D4-metabolizing enzyme of rat leukocytes, which catalyzes the conversion of leukotriene D4 to leukotriene E4

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1987

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Research paper thumbnail of 低栄養若年女性における血清中の銅，ヒスチジン濃度の動態と過酸化脂質形成に対する銅錯体の影響

Nippon Eiseigaku Zasshi (Japanese Journal of Hygiene), 2004

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Research paper thumbnail of ヒト好中球ＩＶ型コラーゲン接着分子の分離同定

Ensho, 1995

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Research paper thumbnail of Comparative studies on the platelet-derived growth factor-A and -B gene expression in human monocytes

Comparative Biochemistry and Physiology Part B: Comparative Biochemistry, 1991

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Research paper thumbnail of VEGF regulates the proliferation of acid-exposed alveolar lining epithelial cells

Thorax, 2003

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Research paper thumbnail of Comparative studies on the leucine aminopeptidase activity of different types of leukocytes

Comparative Biochemistry and Physiology Part B: Comparative Biochemistry, 1984

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Research paper thumbnail of Effect of vitamin K3 on macrophage functions and intracellular calcium

Comparative Biochemistry and Physiology Part A: Physiology, 1988

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Research paper thumbnail of Messenger RNA Expression for Growth Factors in Glomeruli from Focal Glomerular Sclerosis

Clinical Immunology and Immunopathology, 1993

Focal glomerular sclerosis was induced in rats by chronic injections of puromycin aminonucleoside... more Focal glomerular sclerosis was induced in rats by chronic injections of puromycin aminonucleoside (PAN) on Days 0, 27, 34, and 41 and by unilateral nephrectomy on Day 22. Rats were sacrificed on Days 0, 8, and 20 (acute phase) and on Days 48, 60, and 80 (sclerotic phase). The percentage of sclerosing glomeruli was 16.6% on Day 48 and increased significantly to 72.8% on Day 80. We examined glomerular mRNA levels for proliferating cell nuclear antigen (PCNA), platelet-derived growth factor (PDGF)-A and B chains, transforming growth factor (TGF)-beta, epidermal growth factor (EGF), insulin-like growth factor (IGF)-I, and basic fibroblast growth factor (bFGF) on Days 0, 8, 20, 48, 60, and 80. Although these growth factor mRNA levels showed little change in glomeruli until Day 20, all growth factor mRNA levels increased in glomeruli during the sclerotic phase of PAN nephrosis as glomerular sclerosis progressed. On Day 80, mRNA levels for PCNA, PDGF-A and B chains, TGF-beta, EGF, IGF-I, and bFGF increased 12-, 10-, 12-, 15-, 2-, 2-, and 8-fold, respectively, in the glomeruli of PAN-treated rats with marked glomerular sclerosis when compared with control rats. Unilateral nephrectomy without PAN administration did not cause glomerular sclerosis up to Day 80 and mRNA levels for PCNA, PDGF-A and -B chains, TGF-beta, EGF, IGF-I, and bFGF in this group were almost the same as those in the normal sham-operated group. These data suggest that changes in growth factor mRNA levels in glomeruli may contribute to the development of PAN-induced glomerular sclerosis.

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Research paper thumbnail of これから求められる卒前医学教育と大学院教育および臨床研修のあり方

Juntendo Medical Journal, 2012

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Research paper thumbnail of The Relationship Between the Perioperative Transition of Serum Anticholinergic Activity and Postoperative Delirium in Patients Undergoing Esophagectomy and Gastrectomy

Juntendo Medical Journal, 2014

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Research paper thumbnail of Combination of antithrombin and recombinant thrombomodulin modulates neutrophil cell-death and decreases circulating DAMPs levels in endotoxemic rats

Thrombosis Research, 2014

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Research paper thumbnail of Candida albicans proteinase is chemotactic for human peripheral neutrophils and lymphocytes

Journal of Dermatological Science, 1994

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Research paper thumbnail of Synergistic effect of antibacterial agents human β-defensins, cathelicidin LL-37 and lysozyme against Staphylococcus aureus and Escherichia coli

Journal of Dermatological Science, 2005

The antimicrobial properties of the skin are attributed to several agents including human beta-de... more The antimicrobial properties of the skin are attributed to several agents including human beta-defensins (hBDs), cathelicidin LL-37 and skin lysozyme. Although these antibacterial agents reside in the skin to protect it against infection, it is not well known whether the total analysis of all combinations of these agents may result in synergistic effect to enhance their antibacterial activities against invading microorganisms. To elucidate the interactions between keratinocyte-derived antibacterial agents in the extracellular milieu, we investigated the individual and synergistic activities of hBDs, LL-37 and lysozyme against Staphylococcus aureus and Escherichia coli in neutral and acidic milieus. The colorimetric method using alamarBlue was employed to assess the antibacterial activities of hBD-1, -2, -3, LL-37 and lysozyme and the viability of bacteria was read spectrophotometrically. In both neutral and acidic pH milieus, hBD-1, -2, -3, LL-37 and lysozyme exhibited antibacterial activity against S. aureus and E. coli in a dose-dependent manner. Interestingly, the antibacterial activity of hBD-1, -2, -3 and lysozyme but not LL-37 was significantly enhanced in acidic milieu (pH 4.6). Furthermore, various combinations of above agents resulted in a synergistic or additive antibacterial effect against S. aureus and E. coli in neutral milieu. The synergistic effect of hBDs, LL-37 and lysozyme against S. aureus was further significantly enhanced in acidic milieu. In contrast, above antibacterial agents exhibited mainly additive rather than synergistic effect on antibacterial activity against E. coli in acidic milieu. Taken together, these results provide a novel evidence of antimicrobial mechanism of natural human skin-derived antibacterial agents against bacterial infection, and their involvement in innate immunity.

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Research paper thumbnail of Inhibition of the accumulation of macrophages and the generation of macrophage chemotactic activity by dexamethasone in concanavalin A-induced peritonitis of mice

Agents and Actions, 1988

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Research paper thumbnail of Activated peritoneal macrophages inhibit the proliferation of rat ascites hepatoma AH-130 cells via the production of tumor necrosis factor- α and nitric oxide

Inflammation Research, Oct 1, 2000

To study the effect of peritoneal macrophages on tumor cell proliferation, we cultured ascites he... more To study the effect of peritoneal macrophages on tumor cell proliferation, we cultured ascites hepatoma AH-130 cells with unstimulated, or lipopolysaccharide (LPS)- or interleukin (IL)-2-stimulated rat peritoneal macrophages, and examined the proliferation of AH-130 cells. Rat peritoneal macrophages isolated from male Wistar rats were co-cultured with AH-130 cells in the absence or presence of LPS or IL-2. After incubation, proliferation of AH-130 cells was analyzed using flow cytometry. In addition, the levels of tumor necrosis factor (TNF)-alpha and nitric oxide (NOx, nitrate + nitrite) in the culture supernatants were measured. Furthermore, anti-TNF-alpha antibody (10 microg/ml) and nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA, 100 microM) were added to the coculture, and their effect on AH-130 cell proliferation was examined. When AH-130 cells were co-cultured with unstimulated peritoneal macrophages, proliferation of AH-130 cells was not affected. In contrast, when AH-130 cells were cocultured with peritoneal macrophages in the presence of LPS (0.1-20 microg/ml) or IL-2 (1-200 U/ml), proliferation of AH130 cells was dose-dependently suppressed by LPS or IL-2. Moreover, LPS- or IL-2-stimulation increased the levels of TNF-alpha and NOx in the supernatants of AH-130 cell and macrophage co-culture, although LPS and IL-2 did not induce TNF-alpha and NOx production by AH-130 cells incubated without macrophages. Interestingly, anti-TNF-alpha antibody and L-NMMA significantly inhibited the suppression of AH-130 cell proliferation by LPS- or IL-2-stimulated macrophages (p < 0.05). Furthermore, exogenously added recombinant rat TNF-alpha (0.26-1300 ng/ml) or NO donor (GSNO, S-nitroso-L-glutathione) (0.1 - 10 mM) dose-dependently suppressed the proliferation of AH-130 cells in the absence of macrophages. Together these observations suggest that when peritoneal macrophages are activated by LPS and IL-2, they suppress the proliferation of ascites hepatoma AH-130 cells via the production of TNF-alpha and nitric oxide.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Phytochemicals and Vitamin D for a Healthy Life and Prevention of Diseases

International Journal of Molecular Sciences

A variety of phytocompounds contained in medical plants have been used as medication, including K... more A variety of phytocompounds contained in medical plants have been used as medication, including Kampo (traditional Japanese) medicine. Phytochemicals are one category of the chemical compounds mainly known as antioxidants, and recently, their anti-inflammatory effects in preventing chronic inflammation have received much attention. Here, we present a narrative review of the health-promotion and disease-prevention effects of phytochemicals, including polyphenols, the latter of which are abundant in onions, oranges, tea, soybeans, turmeric, cacao, and grapes, along with the synergetic effects of vitamin D. A phenomenon currently gaining popularity in Japan is finding non-disease conditions, so-called ME-BYO (mibyou) and treating them before they develop into illnesses. In addition to lifestyle-related diseases such as metabolic syndrome and obesity, dementia and frailty, commonly found in the elderly, are included as underlying conditions. These conditions are typically induced by chr...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Consumption of yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 augments serum antibody titers against seasonal influenza vaccine in healthy adults

Bioscience of Microbiota, Food and Health

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Research paper thumbnail of Lipopolysaccharides and Cellular Senescence: Involvement in Atherosclerosis

International Journal of Molecular Sciences

Atherosclerosis is a chronic inflammatory disease of the vascular walls related to aging. Thus fa... more Atherosclerosis is a chronic inflammatory disease of the vascular walls related to aging. Thus far, the roles of cellular senescence and bacterial infection in the pathogenesis of atherosclerosis have been speculated to be independent of each other. Some types of macrophages, vascular endothelial cells, and vascular smooth muscle cells are in a senescent state at the sites of atherosclerotic lesions. Likewise, bacterial infections and accumulations of lipopolysaccharide (LPS), an outer-membrane component of Gram-negative bacteria, have also been observed in the atherosclerotic lesions of patients. This review introduces the integration of these two potential pathways in atherosclerosis. Previous studies have suggested that LPS directly induces cellular senescence in cultured monocytes/macrophages and vascular cells. In addition, LPS enhances the inflammatory properties (senescence-associated secretory phenotype [SASP]) of senescent endothelial cells. Thus, LPS derived from Gram-nega...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Evaluation of the effect of administering N-acetyl-glucosamine-containing green tea supplement on biomarkers for cartilage metabolism in healthy individuals without symptoms of arthritis: a randomized double-blind placebo-controlled clinical study

Functional Foods in Health and Disease, 2016

Background: To evaluate the chondroprotective action of an N-acetyl-glucosamine (GlcNAc)-containi... more Background: To evaluate the chondroprotective action of an N-acetyl-glucosamine (GlcNAc)-containing supplement on the joint health of healthy individuals without symptoms of arthritis, we conducted a randomized double-blind placebo-controlled clinical trial. Methods: Subjects (n=100, 51.3 ± 1.0 years (mean ± SE)) without symptoms of arthritis were randomly assigned to receive a 1000 mg GlcNAc-containing diet (GlcNAc group) or a placebo diet (placebo group) once a day for 16 weeks, and the effect on the cartilage metabolism was evaluated by analyzing the ratio of type II collagen degradation to synthesis using type II collagen degradation (C2C) and synthesis (PIICP) markers.Results: The results indicated that the changes in the C2C/PIICP ratios from the baseline were slightly suppressed in the GlcNAc group compared with those in the placebo group at weeks 16 during the intervention and 4 weeks after the intervention. However, there was no significant difference between the two groups...

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Research paper thumbnail of Platelet-derived growth factor-A and -B gene expression during maturation of monocytes to macrophages

Ensho, 1993

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Studies on the leukotriene D4-metabolizing enzyme of rat leukocytes, which catalyzes the conversion of leukotriene D4 to leukotriene E4

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1987

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Research paper thumbnail of 低栄養若年女性における血清中の銅，ヒスチジン濃度の動態と過酸化脂質形成に対する銅錯体の影響

Nippon Eiseigaku Zasshi (Japanese Journal of Hygiene), 2004

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Research paper thumbnail of ヒト好中球ＩＶ型コラーゲン接着分子の分離同定

Ensho, 1995

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Research paper thumbnail of Comparative studies on the platelet-derived growth factor-A and -B gene expression in human monocytes

Comparative Biochemistry and Physiology Part B: Comparative Biochemistry, 1991

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Research paper thumbnail of VEGF regulates the proliferation of acid-exposed alveolar lining epithelial cells

Thorax, 2003

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Research paper thumbnail of Comparative studies on the leucine aminopeptidase activity of different types of leukocytes

Comparative Biochemistry and Physiology Part B: Comparative Biochemistry, 1984

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Effect of vitamin K3 on macrophage functions and intracellular calcium

Comparative Biochemistry and Physiology Part A: Physiology, 1988

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Research paper thumbnail of Messenger RNA Expression for Growth Factors in Glomeruli from Focal Glomerular Sclerosis

Clinical Immunology and Immunopathology, 1993

Focal glomerular sclerosis was induced in rats by chronic injections of puromycin aminonucleoside... more Focal glomerular sclerosis was induced in rats by chronic injections of puromycin aminonucleoside (PAN) on Days 0, 27, 34, and 41 and by unilateral nephrectomy on Day 22. Rats were sacrificed on Days 0, 8, and 20 (acute phase) and on Days 48, 60, and 80 (sclerotic phase). The percentage of sclerosing glomeruli was 16.6% on Day 48 and increased significantly to 72.8% on Day 80. We examined glomerular mRNA levels for proliferating cell nuclear antigen (PCNA), platelet-derived growth factor (PDGF)-A and B chains, transforming growth factor (TGF)-beta, epidermal growth factor (EGF), insulin-like growth factor (IGF)-I, and basic fibroblast growth factor (bFGF) on Days 0, 8, 20, 48, 60, and 80. Although these growth factor mRNA levels showed little change in glomeruli until Day 20, all growth factor mRNA levels increased in glomeruli during the sclerotic phase of PAN nephrosis as glomerular sclerosis progressed. On Day 80, mRNA levels for PCNA, PDGF-A and B chains, TGF-beta, EGF, IGF-I, and bFGF increased 12-, 10-, 12-, 15-, 2-, 2-, and 8-fold, respectively, in the glomeruli of PAN-treated rats with marked glomerular sclerosis when compared with control rats. Unilateral nephrectomy without PAN administration did not cause glomerular sclerosis up to Day 80 and mRNA levels for PCNA, PDGF-A and -B chains, TGF-beta, EGF, IGF-I, and bFGF in this group were almost the same as those in the normal sham-operated group. These data suggest that changes in growth factor mRNA levels in glomeruli may contribute to the development of PAN-induced glomerular sclerosis.

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Research paper thumbnail of これから求められる卒前医学教育と大学院教育および臨床研修のあり方

Juntendo Medical Journal, 2012

Bookmarks Related papers MentionsView impact

Research paper thumbnail of The Relationship Between the Perioperative Transition of Serum Anticholinergic Activity and Postoperative Delirium in Patients Undergoing Esophagectomy and Gastrectomy

Juntendo Medical Journal, 2014

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Combination of antithrombin and recombinant thrombomodulin modulates neutrophil cell-death and decreases circulating DAMPs levels in endotoxemic rats

Thrombosis Research, 2014

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Candida albicans proteinase is chemotactic for human peripheral neutrophils and lymphocytes

Journal of Dermatological Science, 1994

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Synergistic effect of antibacterial agents human β-defensins, cathelicidin LL-37 and lysozyme against Staphylococcus aureus and Escherichia coli

Journal of Dermatological Science, 2005

The antimicrobial properties of the skin are attributed to several agents including human beta-de... more The antimicrobial properties of the skin are attributed to several agents including human beta-defensins (hBDs), cathelicidin LL-37 and skin lysozyme. Although these antibacterial agents reside in the skin to protect it against infection, it is not well known whether the total analysis of all combinations of these agents may result in synergistic effect to enhance their antibacterial activities against invading microorganisms. To elucidate the interactions between keratinocyte-derived antibacterial agents in the extracellular milieu, we investigated the individual and synergistic activities of hBDs, LL-37 and lysozyme against Staphylococcus aureus and Escherichia coli in neutral and acidic milieus. The colorimetric method using alamarBlue was employed to assess the antibacterial activities of hBD-1, -2, -3, LL-37 and lysozyme and the viability of bacteria was read spectrophotometrically. In both neutral and acidic pH milieus, hBD-1, -2, -3, LL-37 and lysozyme exhibited antibacterial activity against S. aureus and E. coli in a dose-dependent manner. Interestingly, the antibacterial activity of hBD-1, -2, -3 and lysozyme but not LL-37 was significantly enhanced in acidic milieu (pH 4.6). Furthermore, various combinations of above agents resulted in a synergistic or additive antibacterial effect against S. aureus and E. coli in neutral milieu. The synergistic effect of hBDs, LL-37 and lysozyme against S. aureus was further significantly enhanced in acidic milieu. In contrast, above antibacterial agents exhibited mainly additive rather than synergistic effect on antibacterial activity against E. coli in acidic milieu. Taken together, these results provide a novel evidence of antimicrobial mechanism of natural human skin-derived antibacterial agents against bacterial infection, and their involvement in innate immunity.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Inhibition of the accumulation of macrophages and the generation of macrophage chemotactic activity by dexamethasone in concanavalin A-induced peritonitis of mice

Agents and Actions, 1988

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