SOCS1/JAB Likely Mediates the Protective Effect of Cardiotrophin-1 Against Lipopolysaccharide-Induced Left Ventricular Dysfunction In Vivo
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- Tanimoto Keiji
- Departments of Medicine and Clinical Science
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- Saito Yoshihiko
- Departments of Medicine and Clinical Science
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- Hamanaka Ichiro
- Departments of Medicine and Clinical Science
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- Kuwahara Koichiro
- Departments of Medicine and Clinical Science
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- Harada Masaki
- Departments of Medicine and Clinical Science
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- Takahashi Nobuki
- Departments of Medicine and Clinical Science
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- Kawakami Rika
- Departments of Medicine and Clinical Science
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- Nakagawa Yasuaki
- Departments of Medicine and Clinical Science
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- Nakanishi Michio
- Departments of Medicine and Clinical Science
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- Adachi Yuichiro
- Departments of Medicine and Clinical Science
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- Shirakami Gotaro
- Anesthesia, Kyoto University Graduate School of Medicine
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- Fukuda Kazuhiko
- Anesthesia, Kyoto University Graduate School of Medicine
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- Yoshimura Akihiko
- Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University
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- Nakao Kazuwa
- Departments of Medicine and Clinical Science
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Abstract
Background Suppressor of cytokine signaling 1 (SOCS1) is a negative regulator of cytokine signaling whose expression is induced in the rat heart by cardiotrophin-1 (CT-1). Sepsis-induced myocardial depression results from the expression of inducible nitric oxide synthase (iNOS) evoked by inflammatory cytokines. Methods and Results The effect of CT-1 on lipopolysaccharide (LPS)-induced cardiac dysfunction was examined in a rat model of sepsis. In the absence of CT-1, LPS (1 mg/kg ip) elicited a reduction of systolic function and dilation of the ventricular cavity within 3-6 h after administration. These physiological effects were accompanied by increased ventricular phosphorylation of signal transducers and activators of transcription (STAT) 1 and STAT3, activation of nuclear factor-κB and expression of iNOS mRNA. Notably, administration of CT-1 (20 μg/kg iv) immediately prior to LPS significantly inhibited all of these LPS-induced changes. To determine whether SOCS1 expression in cardiomyocytes is sufficient to inhibit LPS- and cytokine-induced expression of iNOS mRNA, the effects of forced expression of SOCS1 in cultured neonatal cardiomyocytes were investigated using an adenovirus-mediated transfection system. Forced expression of SOCS1 significantly inhibited iNOS transcription induced by LPS, tumor necrosis factor-α or interferon-γ. Conclusions CT-1-mediated expression of SOCS1 in cardiomyocytes may be a useful target for preventing sepsis-induced myocardial depression. (Circ J 2005; 69: 1412 - 1417)<br>
Journal
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- Circulation Journal
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Circulation Journal 69 (11), 1412-1417, 2005
The Japanese Circulation Society
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Details 詳細情報について
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- CRID
- 1390001205103366912
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- NII Article ID
- 110002703904
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- NII Book ID
- AA11591968
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- ISSN
- 13474820
- 13469843
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- PubMed
- 16247220
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- Text Lang
- en
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- Data Source
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- JaLC
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed