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

Abstract

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.

• Authors: Yulong Hu, Ting Li, Yongmei Wang, Jing Li, Lin Guo, Meiling Wu, Xiaohong Shan, Lingli Que, Tuanzhu Ha, Qi Chen, Jim Kelley, Yuehua Li
• Journal: Frontiers in bioscience (Landmark edition) (Front Biosci (Landmark Ed)) Vol. 14 Issue 7 Pg. 2747-56 (01 01 2009) ISSN: 2768-6698 [Electronic] Singapore
• PMID: 19273233 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• Interleukin-1beta
• Intracellular Signaling Peptides and Proteins
• Myd88 protein, mouse
• Myeloid Differentiation Factor 88
• NF-kappa B
• Tollip protein, mouse
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Base Sequence
• Blotting, Western
• Cardiomegaly (chemically induced, enzymology, metabolism, physiopathology)
• Cells, Cultured
• DNA Primers
• Echocardiography
• Immunoprecipitation
• Interleukin-1beta (pharmacology)
• Intracellular Signaling Peptides and Proteins (genetics, metabolism, physiology)
• Male
• Mice
• Mice, Inbred C57BL
• Myeloid Differentiation Factor 88 (physiology)
• Myocardium (enzymology, metabolism)
• NF-kappa B (metabolism)
• Phosphorylation
• Rats
• Rats, Sprague-Dawley
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction
• p38 Mitogen-Activated Protein Kinases (metabolism)