(Circulation. 1999;99:427-433.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Regulation of CCAAT/Enhancer Binding Protein, Interleukin-6, Interleukin-6 Receptor, and gp130 Expression During Myocardial Ischemia/Reperfusion
From the Division of Cardiology, University of Texas Health Science Center and South Texas Veterans Health Care System, Audie L. Murphy Division, San Antonio, Tex.
Correspondence to Gregory L. Freeman, MD, Division of Cardiology, University of Texas Health Science Center and South Texas Veterans Health Care System, Audie L. Murphy Division, 7703 Floyd Curl Dr, San Antonio, TX 78284-7872. E-mail freeman{at}uthscsa.edu
Background—Interleukin (IL)-6 is
elevated in myocardium after ischemia and
reperfusion. The IL-6 promoter/enhancer region contains response
elements for nuclear factor-
B, AP-1, and CCAAT/enhancer binding
protein (C/EBP). Expression and regulation of C/EBP in rat
myocardium after ischemia and reperfusion has not
been defined, nor has the behavior of the specific IL-6 receptor
(IL-6R) or the signal transducer gp130.
Methods and Results—C/EBP DNA binding activity was not
detected in shams or in previously ischemic tissue at 15
minutes of reperfusion; it was detected at 30 minutes of reperfusion,
increased at 1 hour of reperfusion, and declined by 6 hours of
reperfusion. A supershift was observed with anti–C/EBP-ß but not
with anti-
or anti-
antibodies. mRNA and protein levels of IL-6
and gp130 were detected at low levels in controls, increased at 1 hour
of reperfusion, and remained high until 6 hours of reperfusion. IL-6R
mRNA and protein were not detected in controls, but its mRNA was
induced at 1 hour of reperfusion and its protein at 2 hours of
reperfusion. Although effects of reperfusion were rapid, in
ischemic tissue not reperfused, low levels of C/EBP were
detected at 4 hours, and at 24 hours the levels were slightly elevated.
Significant upregulation in IL-6, IL-6R, and gp130 occurred only at 24
hours of sustained ischemia.
Conclusions—Reperfusion after a brief period of ischemia caused induction of myocardial C/EBP (ß-subunit). The rapid and sustained production of IL-6 with concomitant expression of IL-6 receptor and gp130 suggest that these factors may participate in a local inflammatory cascade after myocardial ischemia and reperfusion.
Key Words: myocardial ischemia • interleukins • receptors • reperfusion
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