Tollip attenuated the hypertrophic response of cardiomyocytes induced by IL-1beta.

We examined the role of Tollip in the hypertrophic response of cardiomyocytes. C57BL/6 mice were subjected to transverse aortic constriction (TAC) for 2 weeks and age-matched sham surgical operated mice served as control. TAC significantly reduced the association of Tollip with IRAK-1 by 66.4 percent and increased NF-kappaB binding activity ...
by 86.5 percent and the levels of phospho-p38 by 114.6 percent in the myocardium compared with sham control, respectively. In vitro experiments showed that IL-1beta stimulation also significantly reduced the association of Tollip with IRAK-1 and increased NF-kappaB binding activity in neonatal cardiomyocytes. Tollip overexpression by transfection of cardiac myocytes significantly attenuated the IL-1beta-induced hypertrophic response of cardiac myocytes as evidenced by reduced cell size (16.4 percent) and decreased ANP expression (33.3 percent). Overexpression of Tollip also reduced NF-kappaB binding activity by 30.7 percent and phospho-p38 by 47.1 percent, respectively. The results suggest that Tollip could be a negative regulator during the development of cardiac hypertrophy. The negative regulation of cardiac hypertrophy by Tollip may involve downregulation of the MyD88-dependent NF-kappaB activation pathway.
Mesh Terms:
Animals, Base Sequence, Blotting, Western, Cardiomegaly, Cells, Cultured, DNA Primers, Echocardiography, Immunoprecipitation, Interleukin-1beta, Intracellular Signaling Peptides and Proteins, Male, Mice, Mice, Inbred C57BL, Myeloid Differentiation Factor 88, Myocardium, NF-kappa B, Phosphorylation, Rats, Rats, Sprague-Dawley, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, p38 Mitogen-Activated Protein Kinases
Front. Biosci.
Date: Mar. 11, 2009
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