Tollip Attenuated the Hypertrophic Response of Cardiomyocytes Induced by IL-1beta
Document Type
Article
Publication Date
1-1-2009
Description
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 phosphop38 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 NFkappaB 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 NFkappaB 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.
Citation Information
Hu, Yulong; Li, Ting; Wang, Yongmei; Li, Jing; Guo, Lin; Wu, Meiling; Shan, Xiaohong; Que, Lingli; Ha, Tuanzhu; Chen, Qi; Kelley, Jim; and Li, Yuehua. 2009. Tollip Attenuated the Hypertrophic Response of Cardiomyocytes Induced by IL-1beta. Frontiers in Bioscience. Vol.14(7). 2747-2756. https://doi.org/10.2741/3411 PMID: 19273233 ISSN: 1093-9946