SOCS1/JAB likely mediates the protective effect of cardiotrophin-1 against lipopolysaccharide-induced left ventricular dysfunction in vivo

Keiji Tanimoto, Yoshihiko Saito, Ichiro Hamanaka, Koichiro Kuwahara, Masaki Harada, Nobuki Takahashi, Rika Kawakami, Yasuaki Nakagawa, Michio Nakanishi, Yuichiro Adachi, Gotaro Shirakami, Kazuhiko Fukuda, Akihiko Yoshimura, Kazuwa Nakao

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 languageEnglish
Pages (from-to)1412-1417
Number of pages6
JournalCirculation Journal
Volume69
Issue number11
DOIs
Publication statusPublished - 2005
Externally publishedYes

Fingerprint

Left Ventricular Dysfunction
Lipopolysaccharides
Cytokines
Nitric Oxide Synthase Type II
Cardiac Myocytes
Sepsis
STAT1 Transcription Factor
Messenger RNA
Ventricular Function
cardiotrophin 1
Adenoviridae
Interferons
Transfection
Dilatation
Tumor Necrosis Factor-alpha
Phosphorylation

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 journalArticle

Tanimoto, K, Saito, Y, Hamanaka, I, Kuwahara, K, Harada, M, Takahashi, N, Kawakami, R, Nakagawa, Y, Nakanishi, M, Adachi, Y, Shirakami, G, Fukuda, K, Yoshimura, A & Nakao, K 2005, 'SOCS1/JAB likely mediates the protective effect of cardiotrophin-1 against lipopolysaccharide-induced left ventricular dysfunction in vivo', Circulation Journal, vol. 69, no. 11, pp. 1412-1417. https://doi.org/10.1253/circj.69.1412
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. / SOCS1/JAB likely mediates the protective effect of cardiotrophin-1 against lipopolysaccharide-induced left ventricular dysfunction in vivo. In: Circulation Journal. 2005 ; Vol. 69, No. 11. pp. 1412-1417.
@article{2b6865b0dacf464c845d7c211a9dfc06,
title = "SOCS1/JAB likely mediates the protective effect of cardiotrophin-1 against lipopolysaccharide-induced left ventricular dysfunction in vivo",
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.",
keywords = "Cardiotrophin-1, Lipopolysaccharide, Sepsis, SOCS1/JAB",
author = "Keiji Tanimoto and Yoshihiko Saito and Ichiro Hamanaka and Koichiro Kuwahara and Masaki Harada and Nobuki Takahashi and Rika Kawakami and Yasuaki Nakagawa and Michio Nakanishi and Yuichiro Adachi and Gotaro Shirakami and Kazuhiko Fukuda and Akihiko Yoshimura and Kazuwa Nakao",
year = "2005",
doi = "10.1253/circj.69.1412",
language = "English",
volume = "69",
pages = "1412--1417",
journal = "Circulation Journal",
issn = "1346-9843",
publisher = "Japanese Circulation Society",
number = "11",

}

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 -