Cardiac Myocytes Produce Interleukin-6 in Culture and in Viable Border Zone of Reperfused Infarctions
Open Access
- 2 February 1999
- journal article
- other
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 99 (4), 546-551
- https://doi.org/10.1161/01.cir.99.4.546
Abstract
Background—Previous work from our laboratory demonstrated that interleukin (IL)-6 plays a potentially critical role in postreperfusion myocardial injury and is the major cytokine responsible for induction of intracellular adhesion molecule (ICAM)-1 on cardiac myocytes during reperfusion. Myocyte ICAM-1 induction is necessary for neutrophil-associated myocyte injury. We have previously demonstrated the induction of IL-6 in the ischemic myocardium, and the current study addresses the cells of origin of IL-6.Methods and Results—In the present study, we combined Northern blot analysis and in situ hybridization to demonstrate IL-6 gene expression in cardiac myocytes. Isolated ventricular myocytes were stimulated with tumor necrosis factor-α, IL-1β, lipopolysaccharide, preischemic lymph, and postischemic lymph. Unstimulated myocytes showed no significant IL-6 mRNA expression. Myocytes stimulated with preischemic lymph showed minimal or no IL-6 mRNA expression, whereas myocytes stimulated with tumor necrosis factor-α, IL-1β, lipopolysaccharide, or postischemic lymph showed a strong IL-6 mRNA induction. Northern blot with ICAM-1 probe revealed ICAM-1 expression under every condition that demonstrated IL-6 induction. We then investigated the expression of IL-6 mRNA in our canine model of ischemia and reperfusion. Cardiac myocytes in the viable border zone of a myocardial infarction exhibited reperfusion-dependent expression of IL-6 mRNA within 1 hour after reperfusion. Mononuclear cells infiltrate the border zone and express IL-6 mRNA.Conclusions—Isolated cardiac myocytes produce IL-6 mRNA in response to several cytokines as well as postischemic cardiac lymph. In addition to its production by inflammatory cells, we demonstrate that IL-6 mRNA is induced in myocytes in the viable border zone of a myocardial infarct. The potential roles of IL-6 in cardiac myocytes in an infarct border are discussed.Keywords
This publication has 36 references indexed in Scilit:
- Signals through gp130 upregulate bcl-x gene expression via STAT1-binding cis-element in cardiac myocytes.JCI Insight, 1997
- Role of early reperfusion in the induction of adhesion molecules and cytokines in previously ischemic myocardiumMolecular and Cellular Biochemistry, 1995
- Cytokine signal transductionCell, 1994
- Interleukin-6 (IL-6) as a mediator of stunned myocardiumThe American Journal of Cardiology, 1993
- Neutrophil induced oxidative injury of cardiac myocytes. A compartmented system requiring CD11b/CD18-ICAM-1 adherence.JCI Insight, 1992
- Negative Inotropic Effects of Cytokines on the Heart Mediated by Nitric OxideScience, 1992
- Serum interleukin 6 levels become elevated in acute myocardial infarctionJournal of Molecular and Cellular Cardiology, 1992
- Adherence of neutrophils to canine cardiac myocytes in vitro is dependent on intercellular adhesion molecule-1.JCI Insight, 1991
- Improved thrombolysis with a modified dose regimen of recombinant tissue-type plasminogen activatorJournal of the American College of Cardiology, 1989
- Blood flow measurements with radionuclide-labeled particlesProgress in Cardiovascular Diseases, 1977