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Featured researches published by Katsuhiro Zen.


Journal of Biological Chemistry | 1999

NF-κB Activation Is Required for Human Endothelial Survival during Exposure to Tumor Necrosis Factor-α but Not to Interleukin-1β or Lipopolysaccharide

Katsuhiro Zen; Aly Karsan; April Stempien-Otero; Esther Yee; Joan Tupper; Xianwu Li; Thomas Eunson; Mark A. Kay; Christopher B. Wilson; Robert K. Winn; John M. Harlan

In the presence of a protein synthesis inhibitor, cycloheximide, tumor necrosis factor-α (TNF-α), interleukin 1-β (IL-1β), or lipopolysaccharide (LPS) induces human umbilical vein endothelial cells (HUVECs) to undergo apoptosis, suggesting that constitutive or inducible cytoprotective pathways are required for cell survival. We studied the correlation between nuclear factor-κB (NF-κB) activation and cell death induced by TNF-α, IL-1β, or LPS. Adenovirus-mediated overexpression of a dominant-negative IκBα (inhibitor of κB) mutant blocked NF-κB activation by gel shift assay and blocked induction of vascular cell adhesion molecule-1 protein by TNF-α, IL-1β, and LPS, a NF-κB-dependent response. In cells overexpressing the IκBα mutant, TNF-α induced cell death, whereas IL-1β or LPS did not. We conclude that cell survival following TNF-α stimulation is NF-κB-dependent but that a constitutive or inducible NF-κB-independent pathway(s) protects IL-1β- or LPS-treated HUVECs from cell death.


Immunobiology | 1996

Monocyte-Derived Macrophages Prime Peripheral T Cells to Undergo Apoptosis by Cell-Cell Contact via ICAM -1 /LFA-1-Dependent Mechanism

Katsuhiro Zen; Junichi Masuda; Jun Ogata

We designed the present study to clarify the mechanism of superantigen-induced apoptosis of human mature T cells and to elucidate the pivotal roles of monocyte-derived macrophages in induction of T cell apoptosis. Exposure of unfractionated human peripheral blood mononuclear cells to SEA, SEB or PHA elicited apoptosis in T cells after 5-day culture. In purified T cell preparations, SEB was unable to induce apoptosis, but was inductive when the purified T cells were cocultured with monocyte-derived macrophages adhering to plastic culture dishes. Placing the T cells in the insert wells which physically separated them from the adhering macrophages resulted in a complete loss of SEB-induced apoptosis. The addition of blocking antibodies against LFA-1, ICAM-1 and CD2 to the cocultures significantly inhibited the SEB-induced T cell apoptosis. We concluded therefore that direct contact of macrophages with T cells is critical in SEB-induced T cell apoptosis, and that adhesion molecules such as LFA-1/ICAM-1 and CD2 may be involved in the mechanism of this effect.


Atherosclerosis | 1992

Interferon-γ suppresses PDGF production from THP-1 cells and blood monocyte-derived macrophages

Chiya Kosaka; Junichi Masuda; Kentaro Shimokado; Katsuhiro Zen; Tasuku Yokota; Toshiyuki Sasaguri; Jun Ogata

Abstract Involvement of the immunological mechanisms in atherogenesis has recently been suggested by immunohistological detection of macrophages and T lymphocytes in atherosclerotic lesions. In the present study, we have investigated the regulatory effect of interferon-γ (IFN-γ), a cytokine secreted by activated T cells, on the production and secretion of platelet-derived growth factor (PDGF) from macrophages in culture. The human monocytic leukemia cell line, THP-1, was treated with phorbol 12-myristate 13-acetate (PMA) for 24 h to induce macrophage differentiation and PDGF production, and then various doses of recombinant human IFN-γ (0–1000 I.U./ml) were added to the culture. After 48 h, the conditioned medium and the cells were harvested and analyzed for PDGF production. PDGF-dependent mitogenic activity in the conditioned medium, estimated by neutralization of mitogenic activity with anti-PDGF antibody, was suppressed by IFN-γ treatment. Radioimmunoassays for PDGF also revealed a decrease in both PDGFAA and -BB in the conditioned medium with IFN-γ treatment, whereas neither total cell DNA as an indication of cell number nor overall protein synthesis based on [ 3 H]leucine incorporation were decreased. Northern analysis of total RNA extracted from the cells demonstrated that IFN-γ suppressed the level of PDGF mRNA. Analysis of mRNA degradation in the presence of actinomycin D demonstrated that the decrease in PDGF mRNA was not due to enhanced degradation of mRNA. A similar inhibitory effect of IFN-γ on PDGF mRNA levels was also found in monocyte-derived macrophages cultured in the presence of granulocyte-macrophage colony stimulating factor. These results suggest that IFN-γ modulates production and secretion of PDGF from macrophages and that the functions of macrophages in atherogenesis may be regulated by the cellular interactions between T cells and macrophages through the action of cytokines such as IFN-γ.


Atherosclerosis | 1994

Tyrosine kinase inhibitors inhibit multiple steps of the cell cycle of vascular smooth muscle cells

Kentaro Shimokado; Katsuhiro Zen; Chiya Kosaka; Toshiyuki Sasaguri; Junichi Masuda; Jun Ogata

Protein tyrosine kinase (PTK) inhibitors have been reported to inhibit proliferation of vascular smooth muscle cells (SMC). To elucidate the mode of this inhibition, the effects on the cell cycle of cultured vascular SMC of three PTK inhibitors with different modes of action (methyl 2,5-dihydroxycinnamate, genistein, and herbimycin A) were studied. Rat aortic SMC were synchronized to the G0 phase of the cell cycle and then released to proceed through the cell cycle by the addition of platelet-derived growth factor (PDGF), and [3H]thymidine incorporation into DNA was measured. The three PTK inhibitors all inhibited PDGF-induced DNA synthesis in a dose-dependent fashion, with IC50 values of 4.7 +/- 1.4 microM for methyl 2,5-dihydroxycinnamate, 6.7 +/- 2.5 microM for genistein, and 0.17 +/- 0.07 microM for herbimycin A. Time course studies suggested that the agents inhibited early G1 phase but not the G0-G1 transition. the lack of effect on the G0-G1 transition was also supported by the finding that the agents did not inhibit the ligand-induced autophosphorylation of PDGF receptor nor the induction of c-fos mRNA at concentrations which were sufficient to inhibit DNA synthesis. PTK inhibitors inhibited progression of the S phase when they were added to SMC that had been arrested at the G1-S border with hydroxyurea. Methyl 2,5-dihydroxycinnamate also blocked the M phase when it was added to SMC cultured in the presence of 10% fetal calf serum, while genistein and herbimycin A did not inhibit the M phase under the same experimental conditions. In accordance with our previous observation, methyl 2,5-dihydroxycinnamate impaired microtubule networks and formation of the mitotic spindle during the M phase. Our findings indicated that PTK inhibitors inhibit multiple steps of the vascular SMC cell cycle.


Experimental Cell Research | 1998

Lipopolysaccharide-Induced NF-κB Activation in Human Endothelial Cells Involves Degradation of IκBα but Not IκBβ

Katsuhiro Zen; Aly Karsan; Thomas Eunson; Esther Yee; John M. Harlan


FEBS Journal | 1994

Position‐independent, high‐level, and correct regional expression of the rat aldolase C gene in the central nervous system of transgenic mice

Yuji Arai; Susumu Kajihara; Junichi Masuda; Sachiko Oh-ishi; Katsuhiro Zen; Jun Ogata; Tsunehiro Mukai


Annals of the New York Academy of Sciences | 2006

Protein Tyrosine Kinase Inhibitors Inhibit Both Proliferation and Chemotaxis of Vascular Smooth Muscle Cellsa

Kentaro Shimokado; Tasuku Yokota; Chiya Kosaka; Katsuhiro Zen; Toshiyuki Sasaguri; Junichi Masuda; Jun Ogata


Experimental Cell Research | 1994

Gene Expression of Monocyte Chemoattractant Protein-1 in Human Monocytes Is Regulated by Cell Density through Protein Tyrosine Kinase and Protein Kinase C

Katsuhiro Zen; Junichi Masuda; Toshiyuki Sasaguri; Chiya Kosaka; Jun Ogata


Annals of the New York Academy of Sciences | 2006

Artery-to-Artery Thromboembolism in Cervicocephalic Arteries and Its Potential Roles in Development of Brain Infarction

Junichi Masuda; Jun Ogata; Katsuhiro Zen; Chiya Kosaka; Toshiyuki Sasaguri; Kentaro Shimokado; Chikao Yutani


Annals of the New York Academy of Sciences | 2006

Protein Kinase C Isoforms that May Mediate G1/S Inhibition in Cultured Vascular Smooth Muscle Cells

Toshiyuki Sasaguri; Chiya Kosaka; Katsuhiro Zen; Junichi Masuda; Kentaro Shimokado; Jun Ogata

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Chiya Kosaka

Kansai Medical University

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Kentaro Shimokado

Tokyo Medical and Dental University

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Esther Yee

University of Washington

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John M. Harlan

University of Washington

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Thomas Eunson

University of Washington

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Aly Karsan

University of British Columbia

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