Masaharu Hatakeyama
Hirosaki University
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Featured researches published by Masaharu Hatakeyama.
The EMBO Journal | 1991
Tadaaki Miyazaki; Mitsuo Maruyama; Yamada G; Masaharu Hatakeyama; Tadatsugu Taniguchi
Recent studies have identified a new family of cytokine receptors, which is primarily characterized by the conservation of periodically interspersed four cysteine residues and the W‐S‐X‐W‐S sequence (‘WS motif’) within the extracellular domain. However, the role of such conserved structures still remains elusive, in particular that of the WS motif. Interleukin‐2 (IL‐2) is known to play a critical role in the clonal expansion of antigen‐stimulated T lymphocytes, and the IL‐2 signal is delivered by one of the receptor components, the IL‐2 receptor beta (IL‐2R beta) chain. The IL‐2R beta chain, unlike the IL‐2R alpha chain, belongs to this receptor family. In the present study, we analyzed the function of the WS motif of IL‐2R beta (Trp194‐Ser195‐Pro196‐Trp197‐Ser198) with the use of site‐directed mutagenesis. Our results indicate the critical role of the two Trp residues in the proper folding of the IL‐2R beta extracellular domain and point to the general functional importance of the WS motif in the new cytokine receptor family.
Endothelium-journal of Endothelial Cell Research | 2004
Tadaatsu Imaizumi; Masaharu Hatakeyama; Koji Yamashita; Hidemi Yoshida; Akira Ishikawa; Kageaki Taima; Kei Satoh; Fumiaki Mori; Koichi Wakabayashi
Interferon-γ (IFN-γ) induces expression of multiple genes in endothelial cells. Retinoic acid–inducible gene-I (RIG-I) encodes a protein belonging to the DExH-box family, but details of its physiological function are not clear. RIG-I is induced in leukemia cells by retinoic acid and in endothelial cells by lipopolysaccharide. In the present study, the authors found that IFN-γ also induces the expression of RIG-I in human umbilical vein endothelial cells. Induction of RIG-I mRNA by IFN-γ was not altered by the treatment with cycloheximide or interleukin-4. Fluorescent immunostaining and Western blot analysis revealed cytoplasmic distribution of RIG-I. The in situ endothelium in a normal lung tissue was also found to express RIG-I protein. Although the physiological function of RIG-I is still unknown, induction of RIG-I by IFN-γ may play an important role in inflammatory or immunological reactions in endothelial cells.
Endothelium-journal of Endothelial Cell Research | 2005
Tadaatsu Imaizumi; Masaharu Hatakeyama; Koji Yamashita; Akira Ishikawa; Hidemi Yoshida; Kei Satoh; Kageaki Taima; Fumiaki Mori; Koichi Wakabayashi
Viral infection induces various responses in vascular endothelial cells. Polyinosinic-polycytidylic acid (poly IC) is a synthetic double-stranded RNA (dsRNA), and treatment of cells with poly IC mimics the viral infection to the cells. Retinoic acid-inducible gene-I (RIG-I) is a protein belonging to the DExH-box family and designated as a putative RNA helicase. RIG-I is considered to play a role in antiviral responses through the regulation of gene expressions. In the present study, the authors treated human umbilical vein endothelial cells (HUVECs) with poly IC and found that poly IC induced the expression of RIG-I. The poly IC-induced RIG-I expression was inhibited by the preincubation of the cells with 2-aminopurine, an inhibitor of dsRNA-dependent protein kinase (PKR). Immunohistochemical examination revealed high levels of RIG-I immunoreactivity in vascular endothelial cells in the thalamus from rats inoculated with hantavirus. Induction of RIG-I by poly IC may be involved in the antiviral responses in endothelial cells.
Brain Research | 2002
Hidemi Yoshida; Tadaatsu Imaizumi; Kunikazu Tanji; Tomoh Matsumiya; Hirotaka Sakaki; Daisuke Kimura; Xue-Fan Cui; Mika Kumagai; Wakako Tamo; Takeo Shibata; Masaharu Hatakeyama; Yoshihiro Sato; Kei Satoh
Vascular endothelial growth factor (VEGF) is a potent and specific mitogen for vascular endothelial cells. To examine whether platelet-activating factor (PAF) induces the expression of VEGF in human astrocytes, we stimulated cultured normal astrocytes with PAF and performed semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) or real-time quantitative PCR for VEGF mRNA and enzyme-linked immunosorbent assay for VEGF protein. PAF increased the expression of VEGF in astrocytes in time- and dose-dependent manners. After 24-h stimulation, 10 nM PAF increased the levels of VEGF protein in astrocyte-conditioned medium by 1.3-fold. When the cells were subjected to hypoxia, the PAF-induced production of VEGF was enhanced by 6.7-fold as compared to the unstimulated cells incubated under normoxia. Dexamethasone was found to inhibit the enhanced VEGF production in response to the stimulation with PAF under hypoxia. We conclude that PAF induces VEGF gene expression in human astrocytes, and the PAF-induced increase in the expression of VEGF may modulate nervous tissue injury due to hypoxia.
Immunology and Cell Biology | 2002
Tadaatsu Imaizumi; Tomoh Matsumiya; Wakako Tamo; Takeo Shibata; Koji Fujimoto; Mika Kumagai; Hidemi Yoshida; Xue-Fan Cui; Kunikazu Tanji; Masaharu Hatakeyama; Koichi Wakabayashi; Kei Satoh
Peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) is a member of nuclear hormone receptor superfamily, and is known to play a role in various biological processes including inflammatory responses and adipocyte differentiation. CX3CL1/fractalkine is a potent agonist for chemotaxis and adhesion of monocytes and lymphocytes. Endothelial cells produce fractalkine when stimulated with cytokines such as interleukin‐1 (IL‐1), tumour necrosis factor‐α and interferon‐γ (IFN‐γ). We herein report that 15‐deoxy‐n12,14 ‐prostaglandinJ2 (15d‐PGJ2), a PPAR‐γ agonist, inhibits the expression of fractalkine induced by IFN‐γ or IL‐1β in human endothelial cells. Agonist for PPAR‐α (WY14643) or PPAR‐γ (ciglitazone) did not inhibit the cytokine‐inducedfractalkine expression, and the effect of 15d‐PGJ2 maybe independent of PPAR. 15‐Deoxy‐D12,14 prostaglandin J2 also inhibited the adhesion of blood mononuclear cells to endothelial monolayers treated with IFN‐γ or IL‐1β. The data suggest that 15d‐PGJ2 regulates inflammatory reactions, at least in part, through the inhibition of fractalkine expression and leucocyte traffic through the endothelium.
International Archives of Allergy and Immunology | 2003
Tadaatsu Imaizumi; Mika Kumagai; Nozomu Nishi; Mitsuomi Hirashima; Masaharu Hatakeyama; Wakako Tamo; Hidemi Yoshida; Takanori Nakamura; Ken Okumura; Kei Satoh
Background: Galectin-9 is involved in chemotaxis and adhesion of eosinophils, and is induced in vascular endothelial cells by interferon-γ (IFN-γ). 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is a ligand for peroxisome proliferator-activated receptor-γ (PPAR-γ), and known to modulate the expression of various genes. Methods: We have studied the effect of 15d-PGJ2 on the IFN-γ-induced galectin-9 expression in human umbilical vein endothelial cells (HUVEC) in culture. Results: 15d-PGJ2 inhibited the IFN-γ-induced galectin-9 expression in a PPAR-γ-independent manner, and also inhibited the adhesion of EoL-1 cells to an HUVEC monolayer treated with IFN-γ. 15d-PGJ2 partially inhibited IFN-γ-induced phosphorylation of STAT-1 in HUVEC. Conclusions: 15d-PGJ2 may regulate inflammatory reactions through the inhibition of galectin-9 expression.
The Annals of Thoracic Surgery | 2002
Kenji Takahashi; Masahito Minakawa; Norihiro Kondo; Shigeru Oikawa; Masaharu Hatakeyama
BACKGROUND The transdiaphragmatic approach is useful for reoperative coronary artery bypass grafting involving the right coronary artery because it does not require median sternotomy or cardiopulmonary bypass. METHODS Twenty-one patients underwent coronary artery bypass surgery by the transdiaphragmatic approach. The ratio of first operations to reoperations was 7:14. The cause of reoperation was occlusion of a saphenous vein graft in 4 patients, right gastroepiploic artery graft failure in 3 patients, and a new sclerotic lesion in the right coronary artery in 7 patients. When the radial artery or saphenous vein was used, grafting extended from the origin of the gastroduodenal artery to the right coronary artery. RESULTS None of the patients died during surgery. The sites of anastomoses were as follows: right coronary artery in 11 patients, right posterior descending artery in 9 patients, and the atrioventricular node artery in 1 patient. The following types of grafts were used: right gastroepiploic artery in 17 patients, saphenous vein in 2 patients, and radial artery in 2 patients. CONCLUSIONS When reoperative coronary surgery involving the right coronary artery is necessary, the transdiaphragmatic technique is effective because it does not damage patent grafts placed during the primary operation.
The EMBO Journal | 1989
Takeshi Doi; Masaharu Hatakeyama; Susumu Itoh; Tadatsugu Taniguchi
Human lymphotropic virus, HTLV‐1, encodes in its proviral genome a transcriptional activator protein, tax‐1, that may be responsible for the development of virus‐induced adult T cell leukemia (ATL), possibly through the aberrant activation of the genes for interleukin‐2 (IL‐2) and one of its receptor (IL‐2R) components, the IL‐2 receptor alpha‐chain (IL‐2R alpha). In the present study, an expression plasmid containing tax‐1 cDNA under the control of HTLV‐1 LTR was introduced into mouse and human CD4‐positive T cell lines. Analysis of the established cell clones revealed a number of interesting features: (i) a limited fraction of the total cell population (less than 25% in each clone) was positive for IL‐2R alpha; (ii) the IL‐2R alpha expression was not permanent, as the IL‐2R alpha positive and negative cells could convert either way. The experimental data suggest that the observed heterogeneity in IL‐2R alpha expression in the transformants is due to a cell‐cycle‐regulated expression and function of tax‐1. Furthermore, a proportion of the induced IL‐2R in EL‐4 was in high‐affinity form, suggesting the association of the IL‐2R alpha and the IL‐2R beta chain (p70‐75) components.
Inflammation | 2004
Masaharu Hatakeyama; Tadaatsu Imaizumi; Wakako Tamo; Koji Yamashita; Hidemi Yoshida; Ikuo Fukuda; Kei Satoh
Heparin is primarily used as an anticoagulant but has many biological functions as well. It binds with high affinity to a range of cytokines including interferon-γ (IFN-γ) and members of chemokine superfamily. IFN-γ is a proinflammatory cytokine that plays a pivotal role in immune and inflammatory responses; and in endothelial cells, it regulates the expression of fractalkine/CX3CL1 that is a potent agonist for the chemotaxis and adhesion of monocytes and lymphocytes. We have investigated the effect of heparin on the fractalkine expression in human umbilical vein endothelial cells (HUVEC) in culture. HUVEC were treated with ∼100 μg/mL heparin and the expression of the IFN-γ-induced fractalkine mRNA and protein were measured by reverse transcription-PCR and western blotting. The IFN-γ-induced expressions of fractalkine mRNA and protein were inhibited by heparin in a concentration-dependent manner. Heparin also inhibited adhesion of mononuclear cells (MNC) to HUVEC monolayers stimulated with IFN-γ, but it did not inhibit the MNC adhesion to the monolayers stimulated with interleukin-1β. Electrophoretic analysis demonstrated direct binding of heparin to IFN-γ and heparin was found to partially block the binding of IFN-γ to IFN-γ receptor (IFN-γ R). Heparin may play a regulatory role in inflammatory and immune responses by modulating the interaction between leukocytes and the vascular endothelium.
Cytokine | 2003
Takeo Shibata; Tadaatsu Imaizumi; Tomoh Matsumiya; Wakako Tamo; Masaharu Hatakeyama; Hidemi Yoshida; Hirohumi Munakata; Ikuo Fukuda; Kei Satoh
Growth related oncogene protein-alpha (GRO-alpha) is a member of C-X-C chemokine and plays an important role in inflammatory responses. Expression of GRO gene family is regulated by a number of factors at both transcriptional and posttranscriptional levels. In the present study, we have addressed the possible regulation of GRO-alpha expression by ubiquitin-proteasome system. Cultures of human umbilical vein endothelial cells were treated with a proteasome inhibitor, MG132, and the levels of GRO-alpha mRNA were analyzed by reverse transcription-polymerase chain reaction or northern blotting. Levels of GRO-alpha protein in the cell-conditioned medium were determined by enzyme-linked immunosorbent assay. MG132 alone increased the levels of GRO-alpha mRNA and protein; however, it did not affect the GRO-alpha mRNA induced by lipopolysaccharide (LPS) and inhibited the LPS-induced decrease in IkappaB levels. Other proteasome inhibitors, MG115 and lactacystin, also induced the expression of GRO-alpha mRNA. MG132 induced the phosphorylation of p38 MAPK, MEK and JNK. Pretreatment of the cells with SB203580, an inhibitor of p38 MAPK, suppressed the MG132-induced GRO-alpha expression, but pretreatment of the cells with U0126, PD98059 or SP600125, inhibitors of MEK1/2 or JNK, did not influence the effect of MG132. We conclude that MG132 upregulates GRO-alpha expression in vascular endothelial cells, at least in part, through the activation of p38 MAPK.