Inhibition of p38 MAPK decreases myocardial TNF-alpha expression and improves myocardial function and survival in endotoxemia

The role of p38 mitogen-activated protein kinase (MAPK) activation in lipopolysaccharide (LPS)-induced myocardial dysfunction has not been clearly defined. Our aim was to investigate the contribution of p38 MAPK in myocardial tumor necrosis factor-alpha (TNF-alpha) expression, cardiac function and s...

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Bibliographic Details
Published in:Cardiovascular research 2003-10, Vol.59 (4), p.893-900
Main Authors: TIANQING PENG, XIANGRU LU, MING LEI, MOE, Gordon W, QINGPING FENG
Format: Article
Language:English
Subjects:
Acute Disease
Animals
Bacterial diseases
Biological and medical sciences
Endotoxemia - metabolism
Etanercept
General aspects
Imidazoles - pharmacology
Immunoglobulin G - pharmacology
Immunologic Factors - pharmacology
Infectious diseases
Lipopolysaccharides
Male
Medical sciences
Mice
Mice, Inbred C57BL
Mitogen-Activated Protein Kinases - antagonists & inhibitors
Mitogen-Activated Protein Kinases - metabolism
Myocardium - metabolism
p38 Mitogen-Activated Protein Kinases
Phosphorylation
Pyridines - pharmacology
Receptors, Tumor Necrosis Factor
Reverse Transcriptase Polymerase Chain Reaction
RNA - analysis
Signal Transduction
Tumor Necrosis Factor-alpha - analysis
Tumor Necrosis Factor-alpha - genetics
Tumor Necrosis Factor-alpha - metabolism
Ventricular Dysfunction, Left
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Summary:The role of p38 mitogen-activated protein kinase (MAPK) activation in lipopolysaccharide (LPS)-induced myocardial dysfunction has not been clearly defined. Our aim was to investigate the contribution of p38 MAPK in myocardial tumor necrosis factor-alpha (TNF-alpha) expression, cardiac function and survival during acute endotoxemia in mice. Acute endotoxemia was induced by LPS (10 mg/kg, i.p.) in mice. Two hours after LPS treatment, left ventricular (LV) function was assessed. Phosphorylation of p38 MAPK was measured by Western blotting. TNF-alpha mRNA and protein levels were determined by semi-quantitative reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. LPS rapidly increased phosphorylation of p38 MAPK, followed by TNF-alpha mRNA expression and protein expression in the LV myocardium. Pre-treatment of the p38 MAPK inhibitor SB202190 (2 mg/kg, i.p.) decreased TNF-alpha mRNA and protein by 65 and 36%, respectively (P
ISSN:0008-6363
1755-3245
DOI:10.1016/s0008-6363(03)00509-1