Identification of cardiac myocytes as the target of interleukin 11, a cardioprotective cytokine

Kimura, Ryusuke; Maeda, Makiko; Arita, Atsushi; Oshima, Yoshifumi; Obana, Masanori; Ito, Takashi; Yamamoto, Yasuhiro; Mohri, Tomomi; Kishimoto, Tadamitsu; Kawase, Ichiro; Fujio, Yasushi; Azuma, Junichi

doi:10.1016/j.cyto.2007.05.011

Cited by 65 publications

(59 citation statements)

References 29 publications

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“…Optimization of the dose and timing of IL-11 administration was not considered in this study but is an important topic as it may influence the outcome. What formed the basis of the present dosing strategy was the results of our previous IL-11 studies (3)(4)(5). In a study using a mouse myocardial IR injury model, the animals pretreated with 8 μg/kg of IL-11 had a significantly reduced infarct size (4).…”

Section: Discussionmentioning

confidence: 99%

“…Both pre-ischemic and post-ischemic IL-11 administration have bestowed favorable outcomes, thus encouraging us to apply both in the present study (12 and 18 μg/kg, respectively). In the clinical setting, recombinant human IL-11 is used for treatment of post-chemotherapy thrombocytopenia in which the therapeutic dose may be increased up to 50 μg/kg per day without adverse effects (3,4). In a recent report using IL-11 to treat acute myocardial infarction, IL-11 was administered at a dose of 25 μg/kg and no side effects were observed (20).…”

Section: Discussionmentioning

confidence: 99%

“…Although the underlying mechanism remains unclear, evidence from previous works has suggested that IL-11 enhances cellular protection and healing. Recently, we found that cardiomyocytes express a cell surface IL-11 receptor bound to a cytokine-specific transmembrane glycoprotein (gp130) and showed in a murine IR injury model that pretreatment with IL-11 provides protection against IR injury through a preconditioning effect (3). We also demonstrated that IL-11 reduces adverse cardiac remodeling, possesses antiapoptotic features, promotes angiogenesis after myocardial infarction (4), and exhibits a protective post-conditioning effect against IR injury through a signal transducer and activator of transcription protein (STAT3) activation (5).…”

Section: Introductionmentioning

confidence: 99%

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The cardioprotective effect of interleukin-11 against ischemia-reperfusion injury in a heart donor model

Tamura¹,

Kohno²,

Mohri³

et al. 2018

Ann. Cardiothorac. Surg.

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Background: Previously, we have demonstrated the cardioprotective effect of interleukin (IL)-11 in animal models of acute coronary syndrome. In this study, we sought to evaluate its cardioprotective potential during prolonged hypothermic global ischemia and subsequent reperfusion using a rat heart donor model.Methods: IL-11 was administered intravenously 10 minutes before harvesting the rat heart. The hearts were preserved in cold (4 ℃) Krebs-Henseleit buffer for 6 hours, and then attached to a Langendorff perfusion apparatus and reperfused with an oxygenated Krebs-Henseleit solution containing IL-11.Normal saline was used instead of IL-11 in the control group. Functional recovery of the reperfused heart was observed by using a left ventricular balloon. Myocardial cell injury was quantified by measuring the biomarkers collected from the coronary effluent. Apoptotic cells were identified and counted using the terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) staining technique.Results: IL-11 administration improved myocardial function after 6 hours of cold ischemia. Although there were no significant differences in any of the baseline-measured values between the two groups, left ventricular developed pressure (LVDP) and changes in left ventricular pressures (dP/dt) were significantly higher in the IL-11 group at 120-minute reperfusion. The number of TUNEL-labeled cardiomyocytes was also significantly smaller in the IL-11 group. Conclusions:The administration of IL-11 showed a significant recovery of cardiac contractile function after 6 hours of cold ischemia. Our data suggest that it may have significant therapeutic potential for maintaining the functional viability of the heart exposed to prolonged hypothermic global ischemia.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The cardioprotective effect of interleukin-11 against ischemia-reperfusion injury in a heart donor model

Tamura¹,

Kohno²,

Mohri³

et al. 2018

Ann. Cardiothorac. Surg.

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“…Thus, ERKs and PI3 kinase/Akt pathways are likely to play some roles in cardioprotection; however, these two signals are activated in a differential manner, depending on ligands. For example, LIF activates Akt in cardiomyocytes, while IL-11 does not (20). In contrast, the JAK/STAT pathway is strongly activated by any IL-6 family cytokine whose receptor α-subunit is expressed in cardiomyocytes.…”

Section: Stat Proteins and Cardioprotectionmentioning

confidence: 97%

“…Recently we have demonstrated that the IL-11 receptor is expressed in cardiac myocytes and that IL-11 stimulation induces STAT3 activation (20). Pretreatment of IL-11 confers resistance to ischemia/reperfusion injury in murine hearts as a preconditioning effect.…”

Section: Clinical Perspectivementioning

confidence: 99%

Glycoprotein 130 Cytokine Signal as a Therapeutic Target Against Cardiovascular Diseases

et al. 2011

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Abstract. Postnatal cardiomyocytes have only limited capacity of proliferation. Therefore, the myocardium is intrinsically equipped with cardioprotective machineries and protects itself from pathological stresses. One of the most important cardioprotective systems is the signal network of autocrine/paracrine factors, including neurohumoral factors, growth factors, and cytokines. In this review, we focus on the roles of interleukin-6 (IL-6) family cytokines, also known as glycoprotein 130 (gp130) cytokines, in cardioprotection. These cytokines make a complex with their specific cytokine receptor α-subunits. The cytokine-receptor α-subunit complex binds to gp130, a common receptor of the IL-6 family, followed by the activation of JAK/STAT, ERK, and PI3 kinase/Akt pathways. In cardiomyocytes, signals through gp130 promote cell survival and angiogenesis through the JAK/STAT pathway. Activation of gp130 in cardiac stem cells induces their endothelial transdifferentiation, leading to neovascularization. Recently, accumulating evidence has revealed that altered JAK/STAT activity is associated with heart failure, suggesting that the JAK/STAT pathway is a therapeutic target against cardiovascular diseases. Interestingly, activation of the JAK/STAT pathway with interleukin-11 (IL-11) exhibits preconditioning effects in ischemia/reperfusion model. Moreover, IL-11 treatment after coronary ligation prevents cardiac remodeling through the JAK/STAT pathway. Since IL-11 is used for patients with thrombocytopenia, we propose that IL-11 is a candidate cytokine clinically available for cardioprotection therapy.

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Interleukin 6 protects H₂O₂‐induced cardiomyocytes injury through upregulation of prohibitin via STAT3 phosphorylation

Jia¹,

Zhou

Deng

et al. 2012

Cell Biochemistry & Function

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Identification of cardiac myocytes as the target of interleukin 11, a cardioprotective cytokine

Cited by 65 publications

References 29 publications

The cardioprotective effect of interleukin-11 against ischemia-reperfusion injury in a heart donor model

The cardioprotective effect of interleukin-11 against ischemia-reperfusion injury in a heart donor model

Glycoprotein 130 Cytokine Signal as a Therapeutic Target Against Cardiovascular Diseases

Interleukin 6 protects H₂O₂‐induced cardiomyocytes injury through upregulation of prohibitin via STAT3 phosphorylation

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Identification of cardiac myocytes as the target of interleukin 11, a cardioprotective cytokine

Cited by 65 publications

References 29 publications

The cardioprotective effect of interleukin-11 against ischemia-reperfusion injury in a heart donor model

The cardioprotective effect of interleukin-11 against ischemia-reperfusion injury in a heart donor model

Glycoprotein 130 Cytokine Signal as a Therapeutic Target Against Cardiovascular Diseases

Interleukin 6 protects H2O2‐induced cardiomyocytes injury through upregulation of prohibitin via STAT3 phosphorylation

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Interleukin 6 protects H₂O₂‐induced cardiomyocytes injury through upregulation of prohibitin via STAT3 phosphorylation