| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(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
This article has been cited by other articles:
 |
|
 |
|
  K. Venkatachalam, B. Venkatesan, A. J. Valente, P. C. Melby, S. Nandish, J. E. B. Reusch, R. A. Clark, and B. Chandrasekar WISP1, a Pro-mitogenic, Pro-survival Factor, Mediates Tumor Necrosis Factor-{alpha} (TNF-{alpha})-stimulated Cardiac Fibroblast Proliferation but Inhibits TNF-{alpha}-induced Cardiomyocyte Death J. Biol. Chem., May 22, 2009; 284(21): 14414 - 14427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Venkatachalam, S. D. Prabhu, V. S. Reddy, W. H. Boylston, A. J. Valente, and B. Chandrasekar Neutralization of Interleukin-18 Ameliorates Ischemia/Reperfusion-induced Myocardial Injury J. Biol. Chem., March 20, 2009; 284(12): 7853 - 7865. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Mikaelian, D. Coluccio, K. T. Morgan, T. Johnson, A. L. Ryan, E. Rasmussen, R. Nicklaus, C. Kanwal, H. Hilton, K. Frank, et al. Temporal Gene Expression Profiling Indicates Early Up-regulation of Interleukin-6 in Isoproterenol-induced Myocardial Necrosis in Rat Toxicol Pathol, February 1, 2008; 36(2): 256 - 264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Westberg, M. Serlachius, P. Lankila, and L. C. Andersson Hypoxic preconditioning induces elevated expression of stanniocalcin-1 in the heart Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1766 - H1771. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Colston, S. D. de la Rosa, M. Koehler, K. Gonzales, R. Mestril, G. L. Freeman, S. R. Bailey, and B. Chandrasekar Wnt-induced secreted protein-1 is a prohypertrophic and profibrotic growth factor Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1839 - H1846. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Hannenhalli, M. E. Putt, J. M. Gilmore, J. Wang, M. S. Parmacek, J. A. Epstein, E. E. Morrisey, K. B. Margulies, and T. P. Cappola Transcriptional Genomics Associates FOX Transcription Factors With Human Heart Failure Circulation, September 19, 2006; 114(12): 1269 - 1276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Wellner, R. Dechend, J.-K. Park, E. Shagdarsuren, N. Al-Saadi, T. Kirsch, P. Gratze, W. Schneider, S. Meiners, A. Fiebeler, et al. Cardiac gene expression profile in rats with terminal heart failure and cachexia Physiol Genomics, February 10, 2005; 20(3): 256 - 267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Dawn, Y.-T. Xuan, Y. Guo, A. Rezazadeh, A. B. Stein, G. Hunt, W.-J. Wu, W. Tan, and R. Bolli IL-6 plays an obligatory role in late preconditioning via JAK-STAT signaling and upregulation of iNOS and COX-2 Cardiovasc Res, October 1, 2004; 64(1): 61 - 71. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Vassilakopoulos, M. Divangahi, G. Rallis, O. Kishta, B. Petrof, A. Comtois, and S. N. A. Hussain Differential Cytokine Gene Expression in the Diaphragm in Response to Strenuous Resistive Breathing Am. J. Respir. Crit. Care Med., July 15, 2004; 170(2): 154 - 161. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. M. Anstead, B. Chandrasekar, Q. Zhang, and P. C. Melby Multinutrient undernutrition dysregulates the resident macrophage proinflammatory cytokine network, nuclear factor-{kappa}B activation, and nitric oxide production J. Leukoc. Biol., December 1, 2003; 74(6): 982 - 991. [Abstract] [Full Text]
|
|
|
|
|
|
R. M. Crawford, S. Jovanovic, G. R. Budas, A. M. Davies, H. Lad, R. H. Wenger, K. A. Robertson, D. J. Roy, H. J. Ranki, and A. Jovanovic Chronic Mild Hypoxia Protects Heart-derived H9c2 Cells against Acute Hypoxia/Reoxygenation by Regulating Expression of the SUR2A Subunit of the ATP-sensitive K+ Channel J. Biol. Chem., August 15, 2003; 278(33): 31444 - 31455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Z. Simkhovich, P. Marjoram, C. Poizat, L. Kedes, and R. A. Kloner Brief episode of ischemia activates protective genetic program in rat heart: a gene chip study Cardiovasc Res, August 1, 2003; 59(2): 450 - 459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Ancey, E. Menet, P. Corbi, S. Fredj, M. Garcia, C. Rucker-Martin, J. Bescond, F. Morel, J. Wijdenes, J.-C. Lecron, et al. Human cardiomyocyte hypertrophy induced in vitro by gp130 stimulation Cardiovasc Res, July 1, 2003; 59(1): 78 - 85. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Chandrasekar, P. C. Melby, H. M. Sarau, M. Raveendran, R. P. Perla, F. M. Marelli-Berg, N. O. Dulin, and I. S. Singh Chemokine-Cytokine Cross-talk. THE ELR+ CXC CHEMOKINE LIX (CXCL5) AMPLIFIES A PROINFLAMMATORY CYTOKINE RESPONSE VIA A PHOSPHATIDYLINOSITOL 3-KINASE-NF-kappa B PATHWAY J. Biol. Chem., February 7, 2003; 278(7): 4675 - 4686. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Srivastava, B. Chandrasekar, A. Bhatnagar, and S. D. Prabhu Lipid peroxidation-derived aldehydes and oxidative stress in the failing heart: role of aldose reductase Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2612 - H2619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Colston, B. Chandrasekar, and G. L. Freeman A Novel Peroxide-induced Calcium Transient Regulates Interleukin-6 Expression in Cardiac-derived Fibroblasts J. Biol. Chem., June 21, 2002; 277(26): 23477 - 23483. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Chandrasekar, J. B. Smith, and G. L. Freeman Ischemia-Reperfusion of Rat Myocardium Activates Nuclear Factor-{{kappa}}B and Induces Neutrophil Infiltration Via Lipopolysaccharide-Induced CXC Chemokine Circulation, May 8, 2001; 103(18): 2296 - 2302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Chandrasekar, J. F. Nelson, J. T. Colston, and G. L. Freeman Calorie restriction attenuates inflammatory responses to myocardial ischemia-reperfusion injury Am J Physiol Heart Circ Physiol, May 1, 2001; 280(5): H2094 - H2102. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-W. QU, H. WANG, I. G. DE PLAEN, R. A. ROZENFELD, and W. HSUEH Neuronal nitric oxide synthase (NOS) regulates the expression of inducible NOS in rat small intestine via modulation of nuclear factor kappa B FASEB J, February 1, 2001; 15(2): 439 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Saito, C. Patterson, Z. Hu, M. S. Runge, U. Tipnis, M. Sinha, and J. Papaconstantinou Expression and self-regulatory function of cardiac interleukin-6 during endotoxemia Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2241 - H2248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. G. Frangogiannis, L. H. Mendoza, M. L. Lindsey, C. M. Ballantyne, L. H. Michael, C. W. Smith, and M. L. Entman IL-10 Is Induced in the Reperfused Myocardium and May Modulate the Reaction to Injury J. Immunol., September 1, 2000; 165(5): 2798 - 2808. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Murray, S. D. Prabhu, and B. Chandrasekar Chronic {beta}-Adrenergic Stimulation Induces Myocardial Proinflammatory Cytokine Expression Circulation, May 23, 2000; 101(20): 2338 - 2341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Fruhbeck, J. Salvador, B. Chandrasekar, D. H. Mitchell, J. T. Colston, and G. L. Freeman Is Leptin Involved in the Signaling Cascade After Myocardial Ischemia and Reperfusion? Response Circulation, May 9, 2000; 101 (18): e194 - e194. [Full Text] [PDF]
|
|
|
|
|
|
S. D. Prabhu, B. Chandrasekar, D. R. Murray, and G. L. Freeman {beta}-Adrenergic Blockade in Developing Heart Failure : Effects on Myocardial Inflammatory Cytokines, Nitric Oxide, and Remodeling Circulation, May 2, 2000; 101(17): 2103 - 2109. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. O. Nossuli, V. Lakshminarayanan, G. Baumgarten, G. E. Taffet, C. M. Ballantyne, L. H. Michael, and M. L. Entman A chronic mouse model of myocardial ischemia-reperfusion: essential in cytokine studies Am J Physiol Heart Circ Physiol, April 1, 2000; 278(4): H1049 - H1055. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kanda, I. Kobayashi, R. Nagai, M. L. Entman, M. Gwechenberger, K. A. Youker, N. G. Frangogiannis, L. H. Michael, L. H. Mendoza, and C. W. Smith Cardiac Interleukin-6 in Ischemic Myocardium • Response Circulation, February 29, 2000; 101 (8): e86 - e86. [Full Text] [PDF]
|
|
|
|
|
|
E. A. Palmieri, G. Benincasa, F. Di Rella, C. Casaburi, M. G. Monti, G. De Simone, L. Chiariotti, L. Palombini, C. B. Bruni, L. Sacca, et al. Differential expression of TNF-alpha , IL-6, and IGF-1 by graded mechanical stress in normal rat myocardium Am J Physiol Heart Circ Physiol, March 1, 2002; 282(3): H926 - H934. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Takimoto, T. Aoyama, Y. Iwanaga, T. Izumi, Y. Kihara, D. Pennica, and S. Sasayama Increased expression of cardiotrophin-1 during ventricular remodeling in hypertensive rats Am J Physiol Heart Circ Physiol, March 1, 2002; 282(3): H896 - H901. [Abstract] [Full Text] [PDF]
|
|