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Tollip attenuated the hypertrophic response of cardiomyocytes induced by IL-1beta
Yulong Hu1,Ting Li1,Yongmei Wang1,Jing Li1,Lin Guo1,Meiling Wu1,Xiaohong Shan1,Lingli Que1,Tuanzhu Ha1,Qi Chen1,Jim Kelley1,Yuehua Li1
1
Department of Pathophysiology, Nanjing Medical University, Nanjing, 210029, China
DOI: 10.2741/3411 Volume 14 Issue 7, pp.2747-2756
Published: 01 January 2009
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.

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Yulong Hu, Ting Li, Yongmei Wang, Jing Li, Lin Guo, Meiling Wu, Xiaohong Shan, Lingli Que, Tuanzhu Ha, Qi Chen, Jim Kelley, Yuehua Li. Tollip attenuated the hypertrophic response of cardiomyocytes induced by IL-1beta. Frontiers in Bioscience-Landmark. 2009. 14(7); 2747-2756.