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Article ; Online: Isolation and propagation of bovine blood-derived macrophages using a mixed culture with bovine endothelial B46 cells.

Hiramatsu, Kanae / Ikeda, Rina / Kawaji, Satoko / Ueno, Yuichi / Nagata, Reiko / Hayashi, Ken-Go / Iga, Kosuke / Yoshioka, Miyako / Takenouchi, Takato

Cell biology international

2023 Volume 48, Issue 1, Page(s) 76–83

Abstract: Macrophages are innate immune cells with multiple functions such as phagocytosis, cytokine production, and antigen presentation. Since macrophages play critical roles in some bacterial infectious diseases in cattle, including tuberculosis, ... ...

Abstract	Macrophages are innate immune cells with multiple functions such as phagocytosis, cytokine production, and antigen presentation. Since macrophages play critical roles in some bacterial infectious diseases in cattle, including tuberculosis, paratuberculosis, and brucellosis, the in vitro culturing of bovine macrophages is useful for evaluating host-pathogen interactions at the cellular and molecular levels. We have previously reported the establishment of two immortalized bovine liver sinusoidal cell lines, endothelial B46 cells and myofibroblast-like A26 cells (Cell Biology International, 40, 1372-1379, 2016). In this study, we investigated the use of these cell lines as feeder cells that support the proliferation of bovine blood-derived macrophages (BBMs). Notably, the B46 cell line efficiently acts as feeder cells for the propagation of BBMs. Compared with primary cultured vascular endothelial cells, the infinite proliferation ability of B46 cells is more beneficial for preparing confluent feeder layers. In conclusion, this study provides a simple and efficient protocol for the isolation and propagation of BBMs using a primary mixed culture of bovine whole blood with B46 feeder cells. Isolated BBMs are expected to be useful for developing in vitro models for studying the interactions between bovine pathogens and host immune cells.
MeSH term(s)	Cattle ; Animals ; Endothelial Cells ; Macrophages/physiology ; Cell Line ; Phagocytosis ; Feeder Cells
Language	English
Publishing date	2023-11-03
Publishing country	England
Document type	Journal Article
ZDB-ID	1143453-3
ISSN	1095-8355 ; 1065-6995
ISSN (online)	1095-8355
ISSN	1065-6995
DOI	10.1002/cbin.12102
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Article ; Online: Enhanced Exciton-Exciton Collisions in an Ultraflat Monolayer MoSe

Hotta, Takato / Ueda, Akihiko / Higuchi, Shohei / Okada, Mitsuhiro / Shimizu, Tetsuo / Kubo, Toshitaka / Ueno, Keiji / Taniguchi, Takashi / Watanabe, Kenji / Kitaura, Ryo

ACS nano

2020 Volume 15, Issue 1, Page(s) 1370–1377

Abstract: Squeezing bubbles and impurities out of interlayer spaces by applying force through a few-layer graphene capping layer leads to van der Waals heterostructures with the ultraflat structure free from random electrostatic potential arising from charged ... ...

Abstract	Squeezing bubbles and impurities out of interlayer spaces by applying force through a few-layer graphene capping layer leads to van der Waals heterostructures with the ultraflat structure free from random electrostatic potential arising from charged impurities. Without the graphene capping layer, a squeezing process with an AFM tip induces applied-force-dependent charges of Δ
Language	English
Publishing date	2020-12-23
Publishing country	United States
Document type	Journal Article
ISSN	1936-086X
ISSN (online)	1936-086X
DOI	10.1021/acsnano.0c08642
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Article ; Online: Cyclosporine protects from intestinal epithelial injury by modulating butyrate uptake via upregulation of membrane monocarboxylate transporter 1 levels.

Ota, Shinji / Sakuraba, Hirotake / Hiraga, Hiroto / Yoshida, Shukuko / Satake, Miwa / Akemoto, Yui / Tanaka, Nahoko / Watanabe, Rina / Takato, Maeda / Murai, Yasuhisa / Ueno, Kayo / Niioka, Takenori / Hayakari, Makoto / Ishiguro, Yoh / Fukuda, Shinsaku

Biochemistry and biophysics reports

2020 Volume 24, Page(s) 100811

Abstract: Background and aims: A relationship between treatment outcomes and intestinal microbiota in patients with inflammatory bowel diseases has been demonstrated. Cyclosporine treatment leads to rapid improvement in severe ulcerative colitis. We hypothesized ... ...

Abstract	Background and aims: A relationship between treatment outcomes and intestinal microbiota in patients with inflammatory bowel diseases has been demonstrated. Cyclosporine treatment leads to rapid improvement in severe ulcerative colitis. We hypothesized that the potent effects of cyclosporine would be exerted through relationships between intestinal epithelial cells (IECs) and the host microbiota. The present study was designed to elucidate the effects of cyclosporine on monocarboxylate transporter 1 (MCT1) regulation and butyrate uptake by IECs. Methods: Colitis was induced in C57BL6 mice via the administration of 4% dextran sulfate sodium in drinking water, following which body weights, colon lengths, and histological scores were evaluated. To examine the role of butyrate in the protective effects of cyclosporine, MCT1 inhibitor and an antibiotic cocktail was administered and tributyrin (TB; a prodrug of butyrate) was supplemented; MCT1 protein expression and acetylated histone 3 (AcH3) signals in IECs, as well as the MCT1-membrane fraction of Caco-2 cells, were evaluated. To explore butyrate uptake, as s butyrate derivatives, 3-bromopyruvic acid (3-BrPA) and 1-pyrenebutyric acid were used. Results: Treatment with cyclosporine inhibited body weight loss and colon length shortening. However, treatment with MCT1 inhibitor and the antibiotic cocktail negated the efficacy of cyclosporine, whereas TB supplementation restored its protective effect. Furthermore, cyclosporine upregulated MCT1 expression in the membrane and the AcH3 signal in IECs, while also inducing higher anti-inflammatory cytokine production compared to that in the vehicle-treated mice. The transcription level of Conclusion: Cyclosporine treatment modulates butyrate uptake via the post-transcriptional upregulation of membrane MCT1 levels in IECs.
Language	English
Publishing date	2020-10-21
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2831046-9
ISSN	2405-5808 ; 2405-5808
ISSN (online)	2405-5808
ISSN	2405-5808
DOI	10.1016/j.bbrep.2020.100811
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Article ; Online: Wheat-bran autolytic peptides containing a branched-chain amino acid attenuate non-alcoholic steatohepatitis via the suppression of oxidative stress and the upregulation of AMPK/ACC in high-fat diet-fed mice.

Kawaguchi, Takumi / Ueno, Takato / Nogata, Yoichi / Hayakawa, Masako / Koga, Hironori / Torimura, Takuji

International journal of molecular medicine

2017 Volume 39, Issue 2, Page(s) 407–414

Abstract: Whole-wheat intake is known to reduce the risk of metabolic syndrome. However, the active component remains unclear. Recently, we identified bioactive peptides [leucine-arginine-proline (LRP) and leucine-glutamine‑proline (LQP)] from wheat bran autolytic ...

Abstract	Whole-wheat intake is known to reduce the risk of metabolic syndrome. However, the active component remains unclear. Recently, we identified bioactive peptides [leucine-arginine-proline (LRP) and leucine-glutamine‑proline (LQP)] from wheat bran autolytic hydrolysate. The present study aimed to investigate the effects of LRP and LQP on non-alcoholic steatohepatitis (NASH) in a mouse model. We also evaluated the effects of these peptides on oxidative stress and on the AMP-activated protein kinase (AMPK) signaling pathway, two major pathogenic factors of NASH. Seven‑week-old male C57BL/6 mice were fed a high-fat diet for 10 weeks and administered water supplemented with 0.05% LRP, 0.20% LRP, 0.05% LQP, or 0.20% LQP (each n=5) or distilled water (control; n=5) ad libitum. Oxidative stress was evaluated by measuring the serum levels of diacron reactive oxygen metabolite (d-ROM) and biological antioxidant potential (BAP). Hepatic expression of phosphorylated AMPK and phosphorylated acetyl-CoA carboxylase (ACC) were evaluated by immunoblotting. The result showed that non‑alcoholic fatty liver disease activity score was significantly decreased in all types of treatment. Serum d-ROM levels were significantly decreased in the 0.20% LRP group, but not in the 0.05% LRP, 0.05% LQP, and 0.20% LQP groups. Serum BAP levels were significantly increased in the 0.05% LRP and 0.20% LRP groups, but not in the 0.05% LQP and 0.20% LQP groups. Immunoblotting analysis revealed that the expression of phospho-AMPK was increased whereas that of phospho-ACC was decreased in the 0.20% LQP group. In conclusion, we demonstrated that both LRP and LQP alleviated the severity of NASH in a high-fat diet-induced NASH mouse model. In addition, we showed that LRP and LQP modulated oxidative stress and upregulated AMPK/ACC, respectively. Thus, LRP and LQP may constitute clinically applicable therapeutic agents for NASH.
MeSH term(s)	AMP-Activated Protein Kinases/metabolism ; Acetyl-CoA Carboxylase/metabolism ; Amino Acids, Branched-Chain/metabolism ; Animals ; Antioxidants/metabolism ; Body Weight ; Diet, High-Fat/adverse effects ; Disease Models, Animal ; Liver/metabolism ; Liver/pathology ; Male ; Mice ; Non-alcoholic Fatty Liver Disease/etiology ; Non-alcoholic Fatty Liver Disease/metabolism ; Non-alcoholic Fatty Liver Disease/pathology ; Oxidative Stress ; Peptides/chemistry ; Peptides/metabolism ; Reactive Oxygen Species/metabolism ; Triticum/chemistry
Chemical Substances	Amino Acids, Branched-Chain ; Antioxidants ; Peptides ; Reactive Oxygen Species ; AMP-Activated Protein Kinases (EC 2.7.11.31) ; Acetyl-CoA Carboxylase (EC 6.4.1.2)
Language	English
Publishing date	2017-02
Publishing country	Greece
Document type	Journal Article
ZDB-ID	1444428-8
ISSN	1791-244X ; 1107-3756
ISSN (online)	1791-244X
ISSN	1107-3756
DOI	10.3892/ijmm.2016.2831
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Article: Regulation of matrix metalloproteinase-1 and alpha-smooth muscle actin expression by interleukin-1 alpha and tumour necrosis factor alpha in hepatic stellate cells.

Inoue, Asami / Obayashi, Kenichi / Sonoda, Yuka / Nakamura, Anna / Ueno, Takato / Kuhara, Satoru / Tashiro, Kosuke

Cytotechnology

2016 Volume 69, Issue 3, Page(s) 461–468

Abstract: Hepatic stellate cells (HSCs) are key players in liver fibrosis and regeneration via collagen degradation and synthesis. These phenomena involve inflammatory cytokines released from non-parenchymal liver cells such as Kupffer cells. Although the effects ... ...

Abstract	Hepatic stellate cells (HSCs) are key players in liver fibrosis and regeneration via collagen degradation and synthesis. These phenomena involve inflammatory cytokines released from non-parenchymal liver cells such as Kupffer cells. Although the effects of individual cytokines on many cell types have been investigated in various conditions, such as inflammation and tissue fibrosis, investigating the effect of combined cytokines would further our understanding of the regulatory mechanisms in tissue fibrosis. Here, we report the effect of multiple cytokine combinations on primary HSCs. We first examined the effect of individual cytokines and then the simultaneous exposure of different cytokines, including interleukin-6 (IL-6), IL-1 alpha (IL-1α), platelet-derived growth factor (PDGF), tumour necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β), on matrix metalloproteinase-1 (MMP1) gene expression in primary HSCs. We observed that the combination of all five cytokines induced higher levels of MMP1 gene expression. Of these cytokines, TNF-α and IL-1α were found to be the key cytokines for not only inducing MMP1 expression, but also increasing α-smooth muscle actin gene expression. In conclusion, the combined treatment of TNF-α and IL-1α on HSCs had an enhanced effect on the expression of the fibrotic genes, MMP1 and α-smooth muscle actin, so appears to be an important regulator for tissue regeneration. This finding suggests that stimulation with combined anti-fibrotic cytokines is a potential approach in the development of a novel therapy for the recovery of liver fibrosis.
Language	English
Publishing date	2016-01-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	1035772-5
ISSN	0920-9069
ISSN	0920-9069
DOI	10.1007/s10616-016-9948-3
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Article ; Online: Cyclosporine protects from intestinal epithelial injury by modulating butyrate uptake via upregulation of membrane monocarboxylate transporter 1 levels

Shinji Ota / Hirotake Sakuraba / Hiroto Hiraga / Shukuko Yoshida / Miwa Satake / Yui Akemoto / Nahoko Tanaka / Rina Watanabe / Maeda Takato / Yasuhisa Murai / Kayo Ueno / Takenori Niioka / Makoto Hayakari / Yoh Ishiguro / Shinsaku Fukuda

Biochemistry and Biophysics Reports, Vol 24, Iss , Pp 100811- (2020)

2020

Abstract	Background and aims: A relationship between treatment outcomes and intestinal microbiota in patients with inflammatory bowel diseases has been demonstrated. Cyclosporine treatment leads to rapid improvement in severe ulcerative colitis. We hypothesized that the potent effects of cyclosporine would be exerted through relationships between intestinal epithelial cells (IECs) and the host microbiota. The present study was designed to elucidate the effects of cyclosporine on monocarboxylate transporter 1 (MCT1) regulation and butyrate uptake by IECs. Methods: Colitis was induced in C57BL6 mice via the administration of 4% dextran sulfate sodium in drinking water, following which body weights, colon lengths, and histological scores were evaluated. To examine the role of butyrate in the protective effects of cyclosporine, MCT1 inhibitor and an antibiotic cocktail was administered and tributyrin (TB; a prodrug of butyrate) was supplemented; MCT1 protein expression and acetylated histone 3 (AcH3) signals in IECs, as well as the MCT1-membrane fraction of Caco-2 cells, were evaluated. To explore butyrate uptake, as s butyrate derivatives, 3-bromopyruvic acid (3-BrPA) and 1-pyrenebutyric acid were used. Results: Treatment with cyclosporine inhibited body weight loss and colon length shortening. However, treatment with MCT1 inhibitor and the antibiotic cocktail negated the efficacy of cyclosporine, whereas TB supplementation restored its protective effect. Furthermore, cyclosporine upregulated MCT1 expression in the membrane and the AcH3 signal in IECs, while also inducing higher anti-inflammatory cytokine production compared to that in the vehicle-treated mice. The transcription level of MCT1 mRNA in IECs and Caco-2 cells did not increase with cyclosporine treatment; however, cyclosporine treatment increased membrane MCT1 expression in these cells and uptake of butyrate derivative. Conclusion: Cyclosporine treatment modulates butyrate uptake via the post-transcriptional upregulation of membrane MCT1 levels in IECs.
Keywords	Butyrate ; Colitis ; Cyclosporine ; Intestinal epithelial cells ; Monocarboxylate transporter 1 ; Biology (General) ; QH301-705.5 ; Biochemistry ; QD415-436
Subject code	610
Language	English
Publishing date	2020-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article: [Type III procollagen-N-peptide (P III P)].

Ueno, Takato / Tanikawa, Kyuichi

Nihon rinsho. Japanese journal of clinical medicine

2004 Volume 62 Suppl 11, Page(s) 314–316

MeSH term(s)	Humans ; Liver Diseases/blood ; Peptide Fragments/blood ; Procollagen/blood
Chemical Substances	Peptide Fragments ; Procollagen ; procollagen Type III-N-terminal peptide
Language	Japanese
Publishing date	2004-11
Publishing country	Japan
Document type	Journal Article
ZDB-ID	390903-7
ISSN	0047-1852
ISSN	0047-1852
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Article ; Online: Green tea with high-density catechins improves liver function and fat infiltration in non-alcoholic fatty liver disease (NAFLD) patients: a double-blind placebo-controlled study.

Sakata, Ryuichiro / Nakamura, Toru / Torimura, Takuji / Ueno, Takato / Sata, Michio

International journal of molecular medicine

2013 Volume 32, Issue 5, Page(s) 989–994

Abstract: Catechins, a major component of green tea extract, have anti-hyperlipidemic effects. The present study investigated the effects of consumption of green tea with high-density catechins in non-alcoholic fatty liver disease (NAFLD) patients. Seventeen ... ...

Abstract	Catechins, a major component of green tea extract, have anti-hyperlipidemic effects. The present study investigated the effects of consumption of green tea with high-density catechins in non-alcoholic fatty liver disease (NAFLD) patients. Seventeen patients with NAFLD consumed green tea with high-density catechins, low-density catechins or a placebo for 12 weeks in a randomized double-blind study. Ultrasonography and computed tomography (CT) were performed at baseline and after 12 weeks. Serum alanine aminotransferase (ALT) levels and urine 8-isoprostane were monitored and compared to baseline at 4, 8 and 12 weeks. Body fat was significantly decreased in the high-density catechin group compared with the placebo and low-density catechin groups after 12 weeks of consumption. All the patients in the high-density catechin group showed a significantly improved liver-to-spleen CT attenuation ratio compared with the placebo and low-density catechin groups after 12 weeks of consumption. The high-density catechin group significantly decreased serum ALT levels and reduced urinary 8-isoprostane excretion compared with the placebo and low-density catechin group after 12 weeks of consumption. Based on a reduced proportion of body fat as estimated by bioimpedance measurement, increased liver-to-spleen CT attenuation ratio, decreased serum ALT levels and reduced urinary 8-isoprostane excretion, we concluded that 12 weeks of 700 ml per day of green tea containing >1 g catechin improved liver fat content and inflammation by reducing oxidative stress in patients with NAFLD.
MeSH term(s)	Double-Blind Method ; Fatty Liver/drug therapy ; Female ; Humans ; Liver/drug effects ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease ; Plant Extracts/therapeutic use ; Tea/chemistry
Chemical Substances	Plant Extracts ; Tea
Language	English
Publishing date	2013-11
Publishing country	Greece
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	1444428-8
ISSN	1791-244X ; 1107-3756
ISSN (online)	1791-244X
ISSN	1107-3756
DOI	10.3892/ijmm.2013.1503
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Article: Does hepatocellular carcinoma develop after treatment of Wegener's granulomatosis with cyclophosphamide?

Ueno, Takato / Sata, Michio

Internal medicine (Tokyo, Japan)

2003 Volume 42, Issue 5, Page(s) 379–380

MeSH term(s)	Carcinoma, Hepatocellular/chemically induced ; Cyclophosphamide/adverse effects ; Cyclophosphamide/therapeutic use ; Granulomatosis with Polyangiitis/drug therapy ; Humans ; Immunosuppressive Agents/adverse effects ; Immunosuppressive Agents/therapeutic use ; Liver Neoplasms/chemically induced ; Mutagens/adverse effects ; Mutagens/therapeutic use
Chemical Substances	Immunosuppressive Agents ; Mutagens ; Cyclophosphamide (8N3DW7272P)
Language	English
Publishing date	2003-05-30
Publishing country	Japan
Document type	Comment ; Editorial
ZDB-ID	32371-8
ISSN	0918-2918 ; 0021-5120
ISSN	0918-2918 ; 0021-5120
DOI	10.2169/internalmedicine.42.379
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Article: Branched-Chain Amino Acid-Rich Supplements Containing Microelements Have Antioxidant Effects on Nonalcoholic Steatohepatitis in Mice.

Tanaka, Hiroaki / Fukahori, Suguru / Baba, Shinji / Ueno, Takato / Sivakumar, Ramadoss / Yagi, Minoru / Asagiri, Kimio / Ishii, Shinji / Tanaka, Yoshiaki

JPEN. Journal of parenteral and enteral nutrition

2016 Volume 40, Issue 4, Page(s) 519–528

Abstract: Background: The aim of the present study was to elucidate whether the administration of antioxidant-rich nutrients, including branched-chain amino acids (BCAAs), microelements, and vitamins, both alone and in combination, has a positive impact on liver ... ...

Abstract	Background: The aim of the present study was to elucidate whether the administration of antioxidant-rich nutrients, including branched-chain amino acids (BCAAs), microelements, and vitamins, both alone and in combination, has a positive impact on liver function in a nonalcoholic steatohepatitis (NASH) mouse model and identify the mechanisms underlying these effects. Methods: Seven-week-old male KKAy mice fed a methionine- and choline-deficient diet (MCD) for 4 weeks were divided into 7 groups and fed the following planned diets for another 4 weeks: group A (normal diet), group B (MCD; control), group C (MCD with rich microelements), group D (MCD with rich BCAAs), group E (MCD with rich microelements and BCAAs), and group F (MCD with rich microelements, BCAAs, and vitamins). We then conducted biochemical assays, histological analyses, immunohistochemistry for 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 4-hydroxy-2'-nonenal (4-HNE), and Western blotting for insulin glucose signaling, lipid metabolism, and endoplasmic reticulum (ER) stress-related signaling in liver specimens obtained from mice in each group. Results: The morphometric grades of all NASH-related findings and the mean degree of 8-OHdG immunolocalization in groups D-F were significantly lower than those observed in group B. The expression levels of insulin receptor β subunit (IRβ) and p-elF in groups E and F and those of phosphatidyl-inositol 3 kinase (PI3K85), p-AcelCoA, and PERK in group F were similar to those noted in group A. Conclusions: The administration of a combination of antioxidant-rich nutrients, including BCAAs and microelements, is likely to suppress the progression of NASH by reducing oxidative stress, primarily via the downregulation of the ER stress pathway.
Language	English
Publishing date	2016-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	800861-9
ISSN	0148-6071
ISSN	0148-6071
DOI	10.1177/0148607114555160
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