title: 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.affiliation: Department of Pathophysiology, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Hu
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Guo
authors.forename: Meiling
authors.initials: M
authors.lastname: Wu
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Shan
authors.forename: Lingli
authors.initials: L
authors.lastname: Que
authors.forename: Tuanzhu
authors.initials: T
authors.lastname: Ha
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.forename: Jim
authors.initials: J
authors.lastname: Kelley
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D006332:Cardiomegaly / Q000139:chemically induced* / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology; D002478:Cells, Cultured; D017931:DNA Primers; D004452:Echocardiography; D047468:Immunoprecipitation; D053583:Interleukin-1beta / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017931:DNA Primers; D053583:Interleukin-1beta; D047908:Intracellular Signaling Peptides and Proteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C485837:Tollip protein, mouse; D048051:p38 Mitogen-Activated Protein Kinases