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-• B• and expression of iNOS mRNA. Notably, administration of CT-1 (20• g •/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-• •or interferon-•.• Conclusions: CT-1-mediated expression of SOCS1 in cardiomyocytes may be a useful target for preventing sepsis-induced myocardial depression.
| Original language | English |
|---|---|
| Pages (from-to) | 1412-1417 |
| Number of pages | 6 |
| Journal | Circulation Journal |
| Volume | 69 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2005 |
| Externally published | Yes |
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Keywords
- Cardiotrophin-1
- Lipopolysaccharide
- Sepsis
- SOCS1/JAB
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology
Cite this
SOCS1/JAB likely mediates the protective effect of cardiotrophin-1 against lipopolysaccharide-induced left ventricular dysfunction in vivo. / Tanimoto, Keiji; Saito, Yoshihiko; Hamanaka, Ichiro; Kuwahara, Koichiro; Harada, Masaki; Takahashi, Nobuki; Kawakami, Rika; Nakagawa, Yasuaki; Nakanishi, Michio; Adachi, Yuichiro; Shirakami, Gotaro; Fukuda, Kazuhiko; Yoshimura, Akihiko; Nakao, Kazuwa.
In: Circulation Journal, Vol. 69, No. 11, 2005, p. 1412-1417.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - SOCS1/JAB likely mediates the protective effect of cardiotrophin-1 against lipopolysaccharide-induced left ventricular dysfunction in vivo
AU - Tanimoto, Keiji
AU - Saito, Yoshihiko
AU - Hamanaka, Ichiro
AU - Kuwahara, Koichiro
AU - Harada, Masaki
AU - Takahashi, Nobuki
AU - Kawakami, Rika
AU - Nakagawa, Yasuaki
AU - Nakanishi, Michio
AU - Adachi, Yuichiro
AU - Shirakami, Gotaro
AU - Fukuda, Kazuhiko
AU - Yoshimura, Akihiko
AU - Nakao, Kazuwa
PY - 2005
Y1 - 2005
N2 - 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-• B• and expression of iNOS mRNA. Notably, administration of CT-1 (20• g •/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-• •or interferon-•.• Conclusions: CT-1-mediated expression of SOCS1 in cardiomyocytes may be a useful target for preventing sepsis-induced myocardial depression.
AB - 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-• B• and expression of iNOS mRNA. Notably, administration of CT-1 (20• g •/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-• •or interferon-•.• Conclusions: CT-1-mediated expression of SOCS1 in cardiomyocytes may be a useful target for preventing sepsis-induced myocardial depression.
KW - Cardiotrophin-1
KW - Lipopolysaccharide
KW - Sepsis
KW - SOCS1/JAB
UR - http://www.scopus.com/inward/record.url?scp=27644552147&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=27644552147&partnerID=8YFLogxK
U2 - 10.1253/circj.69.1412
DO - 10.1253/circj.69.1412
M3 - Article
VL - 69
SP - 1412
EP - 1417
JO - Circulation Journal
JF - Circulation Journal
SN - 1346-9843
IS - 11
ER -