© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Induction of interleukin (IL)-6 by hypoxia is mediated by nuclear factor (NF)-
B and NF-IL6 in cardiac myocytes
aDepartment of Medicine III, Osaka University Medical School, Suita, Osaka 565-0871, Japan
bDepartment of Biochemistry, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8131, Japan
* Corresponding author. Tel.: +81-6-879-3835; fax: +81-6-879-3839; e-mail: takihara@imed3.med.osaka-u.ac.jp
Objectives: We have previously reported that interleukin (IL)-6 is induced by hypoxic stimulation in cardiac myocytes. In the present study, we examined the induction of potent transcription factors of IL-6, nuclear factor (NF)-
B and NF-IL6, in cardiac myocytes subjected to hypoxia. Methods: Five different lengths of IL-6 promoter-luciferase reporter plasmids and three mutant plasmids, in which the binding sites of NF-B and/or NF-IL6 were disrupted, were transfected into neonatal rat cardiac myocytes. Luciferase activities after hypoxic stimulation were measured. Electrophoretic mobility shift assays were performed using oligonucleotides containing the binding site for NF-B or NF-IL6 as a probe. Results: Hypoxic stimulation for 4 h increased luciferase activity by 5.7 fold in –179/+12-luciferase reporter plasmid, whereas no significant increase was observed in –60/+12-luciferase plasmid. Decrease in luciferase activity was more prominent when the NF-B binding site was disrupted rather than when the NF-IL6 binding site was disrupted. Moreover, when both sites were disrupted, luciferase activity increased only by 1.5 fold. Electrophoretic mobility shift assays demonstrated enhanced binding activity to oligonucleotides containing the NF-B binding site in hypoxic cardiac myocytes, which displayed a supershift with antibody to its subunit, p50 or p65. The binding activity to the NF-IL6 probe also enhanced and displayed a supershift with antibody to NF-IL6. Conclusions: Although hypoxic stimulation induced NF-B and NF-IL6 in cardiac myocytes, NF-B may be the primary positive regulator of transcriptional activation of the IL-6 gene in the context of hypoxia.
KEYWORDS Cardiac myocytes; Hypoxia; Interleukin-6; Gene expression; Nuclear factor-B; Rat
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  N. Burioka, S. Koyanagi, M. Endo, M. Takata, Y. Fukuoka, M. Miyata, K. Takeda, H. Chikumi, S. Ohdo, and E. Shimizu Clock gene dysfunction in patients with obstructive sleep apnoea syndrome Eur. Respir. J., July 1, 2008; 32(1): 105 - 112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. Johnson, C. L. Sherry, J. M. York, and G. G. Freund Acute Hypoxia, Diabetes, and Neuroimmune Dysregulation: Converging Mechanisms in the Brain Neuroscientist, June 1, 2008; 14(3): 235 - 239. [Abstract] [PDF]
|
|
|
|
 |
|
 F. Battaglia, S. Delfino, E. Merello, M. Puppo, R. Piva, L. Varesio, and M. C. Bosco Hypoxia transcriptionally induces macrophage-inflammatory protein-3{alpha}/CCL-20 in primary human mononuclear phagocytes through nuclear factor (NF)-{kappa}B J. Leukoc. Biol., March 1, 2008; 83(3): 648 - 662. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. H. Wang, X. Y. Yang, X. Zhang, and W. L. Farrar Inhibition of adhesive interaction between multiple myeloma and bone marrow stromal cells by PPAR{gamma} cross talk with NF-{kappa}B and C/EBP Blood, December 15, 2007; 110(13): 4373 - 4384. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Yang, M. A. Choudhry, Y.-C. Hsieh, S. Hu, L. W. Rue III, K. I. Bland, and I. H. Chaudry Estrus cycle: influence on cardiac function following trauma-hemorrhage Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2807 - H2815. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. E. Schweppe, T. H. Cheung, and N. G. Ahn Global Gene Expression Analysis of ERK5 and ERK1/2 Signaling Reveals a Role for HIF-1 in ERK5-mediated Responses J. Biol. Chem., July 28, 2006; 281(30): 20993 - 21003. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Koechlin, F Maltais, D Saey, A Michaud, P LeBlanc, M Hayot, and C Prefaut Hypoxaemia enhances peripheral muscle oxidative stress in chronic obstructive pulmonary disease Thorax, October 1, 2005; 60(10): 834 - 841. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Minoguchi, T. Yokoe, T. Tazaki, H. Minoguchi, A. Tanaka, N. Oda, S. Okada, S. Ohta, H. Naito, and M. Adachi Increased Carotid Intima-Media Thickness and Serum Inflammatory Markers in Obstructive Sleep Apnea Am. J. Respir. Crit. Care Med., September 1, 2005; 172(5): 625 - 630. [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]
|
|
|
|
 |
|
 H. Kida, M. Yoshida, S. Hoshino, K. Inoue, Y. Yano, M. Yanagita, T. Kumagai, T. Osaki, I. Tachibana, Y. Saeki, et al. Protective effect of IL-6 on alveolar epithelial cell death induced by hydrogen peroxide Am J Physiol Lung Cell Mol Physiol, February 1, 2005; 288(2): L342 - L349. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Zhong, L. Belardinelli, T. Maa, and D. Zeng Synergy between A2B Adenosine Receptors and Hypoxia in Activating Human Lung Fibroblasts Am. J. Respir. Cell Mol. Biol., January 1, 2005; 32(1): 2 - 8. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Vannay, A. Fekete, C. Adori, T. Toth, G. Losonczy, L. Laszlo, B. Vasarhelyi, T. Tulassay, and A. Szabo Divergence of renal vascular endothelial growth factor mRNA expression and protein level in post-ischaemic rat kidneys Exp Physiol, July 1, 2004; 89(4): 435 - 444. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Yokoe, K. Minoguchi, H. Matsuo, N. Oda, H. Minoguchi, G. Yoshino, T. Hirano, and M. Adachi Elevated Levels of C-Reactive Protein and Interleukin-6 in Patients With Obstructive Sleep Apnea Syndrome Are Decreased by Nasal Continuous Positive Airway Pressure Circulation, March 4, 2003; 107(8): 1129 - 1134. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. S. Chandel, W. C. Trzyna, D. S. McClintock, and P. T. Schumacker Role of Oxidants in NF-{kappa}B Activation and TNF-{alpha} Gene Transcription Induced by Hypoxia and Endotoxin J. Immunol., July 15, 2000; 165(2): 1013 - 1021. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sano, K. Fukuda, T. Sato, H. Kawaguchi, M. Suematsu, S. Matsuda, S. Koyasu, H. Matsui, K. Yamauchi-Takihara, M. Harada, et al. ERK and p38 MAPK, but not NF-{kappa}B, Are Critically Involved in Reactive Oxygen Species-Mediated Induction of IL-6 by Angiotensin II in Cardiac Fibroblasts Circ. Res., October 12, 2001; 89(8): 661 - 669. [Abstract] [Full Text] [PDF]
|
|