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(3): 22, 2015 May.
Article
em En
| MEDLINE
| ID: mdl-25820907
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão Miocárdica
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Transdução de Sinais
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Interleucinas
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Fator de Transcrição STAT3
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Receptor gp130 de Citocina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Basic Res Cardiol
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Taiwan