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

Front Biosci (Landmark Ed). 2009 Jan 1;14:2747-56. doi: 10.2741/3411.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • 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