Regulation of CCAAT/enhancer binding protein, interleukin-6, interleukin-6receptor, and gp130 expression during myocardial ischemia/reperfusion

Background-Interleukin (IL)-6 is elevated in myocardium after ischemia and reperfusion. The IL-6 promoter/enhancer region contains response elements f or nuclear factor-kappa B, AP-1, and CCAAT/enhancer binding protein (C/EBP) , Expression and regulation of C/EBP in rat myocardium after ischemia and r eperfusion 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 detecte d at 30 minutes of reperfusion, increased at 1 hour of reperfusion, and dec lined by 6 hours of reperfusion, A supershift was observed with anti-C/EBP- beta but not with anti-alpha or anti-delta antibodies, mRNA and protein lev els 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, Althou gh effects of reperfusion were rapid, in ischemic tissue not reperfused, lo w 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 occu rred only at 24 hours of sustained ischemia. Conclusions-Reperfusion after a brief period of ischemia caused induction o f myocardial C/EBP (beta-subunit). The rapid and sustained production of IL -6 with concomitant expression of IL-6 receptor and gp130 suggest that thes e factors may participate in a local inflammatory cascade after myocardial ischemia and reperfusion.