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Interleukin-27, a novel cytokine induced by ischemia–reperfusion injury in rat hearts, mediates cardioprotective effects via the gp130/STAT3 pathway

  • Ming-Chieh Ma
  • Bao-Wei Wang
  • Tzu-Pei Yeh
  • Jia-Long Wu
  • Tun-Hui Chung
  • Kochung Tsui
  • Chih-Fan Chiang
  • Ai-Ju Huang
  • Yu-Tzu HuangEmail author
Original Contribution

Abstract

Patients with coronary artery disease show high serum levels of interleukin (IL)-27, a novel member of the IL-6 family. However, the function of IL-27 in hearts suffering ischemia/reperfusion (IR) injury is unclear. Here, we showed increased expression of mRNA for the IL-27 subunits, EBI3 and p28, in rat hearts after 40 min of coronary ligation and release for 7 days. This increase was associated with a peak in the release of the cardiac enzyme, creatine kinase-MB, on day 2 post-release. Moreover, levels of IL-27 receptor subunit gp130 mRNA, but not those of subunit WSX-1 mRNA, decreased in post-ischemic hearts. These results suggest that increased IL-27 production may compensate for receptor downregulation during myocardial recovery. Lactate dehydrogenase release and crystal violet staining revealed that IL-27 or IL-6 significantly attenuated severe hypoxia (SH, 2 % O2)-induced cell damage in H9c2 cardiomyoblasts and primary rat neonatal cardiomyocytes. Incubating cardiomyocytes with IL-27 or IL-6 resulted in time-dependent activation of signal transducers and activators of transcription 3 (STAT3). Interestingly, IL-27-induced STAT3 activation was attenuated by pre-treatment with a gp130-neutralizing antibody. Blocking gp130 also reduced the cytoprotective effects of IL-27 or IL-6. Moreover, IL-27-mediated protection against SH was blocked by stattic, a small-molecule inhibitor of STAT3. IL-27 markedly improved post-ischemic recovery and reduced tissue damage in isolated perfused hearts when administered 5 min before reperfusion. These results indicate that IL-27 protects the myocardium against IR injury and facilitates the recovery of damaged cardiomyocytes via the gp130/STAT3 pathway.

Keywords

IL-27 Cardiomyocytes Hypoxia Ischemia/reperfusion Cell death gp130 STAT3 

Notes

Acknowledgments

This study was supported in part by the Ministry of Science and Technology in Taiwan (96-2320-B-030-002-MY2 and 101-2314-B-030-002-MY3) and was funded by collaboration of the Shin-Kong Wu Ho-Su Memorial Hospital and Fu Jen Catholic University (SKH-FJU-96-13 and SKH-FJU-97-17).

Conflict of interest

None.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Ming-Chieh Ma
    • 1
  • Bao-Wei Wang
    • 2
  • Tzu-Pei Yeh
    • 1
  • Jia-Long Wu
    • 1
  • Tun-Hui Chung
    • 1
  • Kochung Tsui
    • 3
  • Chih-Fan Chiang
    • 1
  • Ai-Ju Huang
    • 1
  • Yu-Tzu Huang
    • 1
    Email author
  1. 1.School of MedicineFu Jen Catholic UniversityNew TaipeiTaiwan
  2. 2.Department of Education and ResearchShin-Kong Wu Ho-Su Memorial HospitalTaipeiTaiwan
  3. 3.Department of Clinical PathologyCathay General HospitalTaipeiTaiwan

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