title: Interleukin-27, a novel cytokine induced by ischemia-reperfusion injury in rat hearts, mediates cardioprotective effects via the gp130/STAT3 pathway.
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.
authors.affiliation: School of Medicine, Fu Jen Catholic University, 510 Chungcheng Road, Hsinchuang District, New Taipei, 24205, Taiwan.
authors.forename: Ming-Chieh
authors.initials: MC
authors.lastname: Ma
authors.forename: Bao-Wei
authors.initials: BW
authors.lastname: Wang
authors.forename: Tzu-Pei
authors.initials: TP
authors.lastname: Yeh
authors.forename: Jia-Long
authors.initials: JL
authors.lastname: Wu
authors.forename: Tun-Hui
authors.initials: TH
authors.lastname: Chung
authors.forename: Kochung
authors.initials: K
authors.lastname: Tsui
authors.forename: Chih-Fan
authors.initials: CF
authors.lastname: Chiang
authors.forename: Ai-Ju
authors.initials: AJ
authors.lastname: Huang
authors.forename: Yu-Tzu
authors.initials: YT
authors.lastname: Huang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D050822:Cytokine Receptor gp130 / Q000378:metabolism*; D004195:Disease Models, Animal; D007378:Interleukins / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D007378:Interleukins; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; C556273:interleukin-27, rat; D050822:Cytokine Receptor gp130