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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

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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.

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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).

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Authors and Affiliations

  1. School of Medicine, Fu Jen Catholic University, 510 Chungcheng Road, Hsinchuang District, New Taipei, 24205, Taiwan

    Ming-Chieh Ma, Tzu-Pei Yeh, Jia-Long Wu, Tun-Hui Chung, Chih-Fan Chiang, Ai-Ju Huang & Yu-Tzu Huang

  2. Department of Education and Research, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

    Bao-Wei Wang

  3. Department of Clinical Pathology, Cathay General Hospital, Taipei, Taiwan

    Kochung Tsui

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  1. Ming-Chieh Ma
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Ma, MC., Wang, BW., Yeh, TP. et al. Interleukin-27, a novel cytokine induced by ischemia–reperfusion injury in rat hearts, mediates cardioprotective effects via the gp130/STAT3 pathway. Basic Res Cardiol 110, 22 (2015). https://doi.org/10.1007/s00395-015-0480-y

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