Tumor necrosis factor-[alpha] induced expression of heat shock
protein 72 in adult feline cardiac myocytes.
Nakano, Masayuki, Anne A. Knowlton, Tomoyuki Yokoyama, Werner
Lesslauer, Douglas L. Mann.
Cardiology Section of the Department of Medicine, Veterans
Administration Medical Center, Baylor College of Medicine, Houston
Texas 77030 and F. Hoffman-La Roche Ltd, Pharmaceutical Research,
Central Nervous System Department, Basel, Switzerland
APStracts 2:0413H, 1995.
Tumor necrosis factor-[alpha] (TNF[alpha]) is a proinflammatory
cytokine that is elaborated in a myriad of cardiac disease states.
Although the biological role for TNF[alpha] 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[alpha] 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[alpha] would modulate the expression of heat shock protein 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[alpha] concentrations (10 - 1000 U/ml) for 12 hours
showed that concentrations of TNF[alpha] < 10 U/ml had no effect
on HSP 72 expression, whereas TNF[alpha] concentrations > 50
U/ml produced significant increases in HSP 72 expression. Continuous
stimulation of cardiac myocytes with a single concentration of
TNF[alpha] (200 U/ml) revealed time-dependent effects on HSP 72
expression: increased HSP 72 expression was detected 3 hours
following cytokine stimulation, peaked by approximately 12 hours, and
then returned toward baseline by 48 hours. 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[alpha] 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[alpha] may enable
the heart to better withstand certain forms of stress.
Received 9 May 1995; accepted in final form 8 September 1995.
APS Manuscript Number H445-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.