Tumor necrosis factor-α-induced expression of heat shock protein 72 in adult feline cardiac myocytes

Masayuki Nakano, Anne A. Knowlton, Tomoyuki Yokoyama, Werner Lesslauer, Douglas L. Mann

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Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine that is elaborated in a myriad of cardiac disease states. Although the biological role for TNF-α in the adult heart is not known, a recent study in fetal myocardial cells has shown that this cytokine increases the synthesis of low- molecular-weight stress proteins. These findings suggested the interesting possibility that TNF-α might play a functional role in the adult heart by increasing the expression of stress proteins in cardiac myocytes. Accordingly, the purpose of this study was to determine whether TNF-α would modulate the expression of heat shock protein 72 (HSP 72), a stress protein that is thought to exert protective effects in the adult heart. Stimulation of adult feline cardiac myocytes with a range of TNF-α concentrations (10- 1,000 U/ml) for 12 h showed that concentrations of TNF-α ≤10 U/ml had no effect on HSP 72 expression, whereas TNF-α concentrations ≥50 U/ml produced significant increases in HSP 72 expression. Continuous stimulation of cardiac myocytes with a single concentration of TNF-α (200 U/ml) revealed time- dependent effects on HSP 72 expression: increased HSP 72 expression was detected 3 h following cytokine stimulation, peaked by ~12 h, and then returned toward baseline by 48 h. Additional studies indicated that stimulation of the type 1 TNF receptor was responsible for the increase in HSP 72 expression. In summary, these studies constitute the initial demonstration that TNF-α exerts concentration- and time-dependent effects on the expression of HSP 72 in the adult mammalian cardiac myocytes, thus suggesting the interesting possibility that the elaboration of TNF-α may enable the heart to better withstand certain forms of stress.

Original languageEnglish
Pages (from-to)H1231-H1239
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number4 39-4
StatePublished - May 13 1996


  • cytokine
  • stress protein


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