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 |
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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 |
Keywords
- Cardiotrophin-1
- Lipopolysaccharide
- SOCS1/JAB
- Sepsis
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine