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J Mol Cell Cardiol. 2015 Dec;89(Pt B):203-13. doi: 10.1016/j.yjmcc.2015.11.004. Epub 2015 Nov 6.

Interleukin-10 inhibits chronic angiotensin II-induced pathological autophagy.

Author information

1
Center for Translational Medicine, Temple University, Philadelphia 19140, USA; Department of Pharmacology, Temple University, Philadelphia 19140, USA. Electronic address: raj.kishore@temple.edu.
2
Department of Cardiovascular Science, Houston Methodist Research Institute, Houston 77030, USA.
3
Center for Translational Medicine, Temple University, Philadelphia 19140, USA.
4
Center for Translational Medicine, Temple University, Philadelphia 19140, USA; Department of Pharmacology, Temple University, Philadelphia 19140, USA.
5
Center for Translational Medicine, Temple University, Philadelphia 19140, USA. Electronic address: suresh.verma@temple.edu.

Abstract

BACKGROUND:

Although autophagy is an essential cellular salvage process to maintain cellular homeostasis, pathological autophagy can lead to cardiac abnormalities and ultimately heart failure. Therefore, a tight regulation of autophagic process would be important to treat chronic heart failure. Previously, we have shown that IL-10 strongly inhibited pressure overload-induced hypertrophy and heart failure, but role of IL-10 in regulation of pathological autophagy is unknown. Here we tested the hypothesis that IL-10 inhibits angiotensin II-induced pathological autophagy and this process, in part, leads to improve cardiac function.

METHODS AND RESULTS:

Chronic Ang II strongly induced mortality, cardiac dysfunction in IL-10 Knockout mice. IL-10 deletion exaggerated pathological autophagy in response to Ang II treatment. In isolated cardiac myocytes, IL-10 attenuated Ang II-induced pathological autophagy and activated Akt/mTORC1 signaling. Pharmacological or molecular inhibition of Akt and mTORC1 signaling attenuated IL-10 effects on Ang II-induced pathological autophagy. Furthermore, lysosomal inhibition in autophagic flux experiments further confirmed that IL-10 inhibits pathological autophagy via mTORC1 signaling.

CONCLUSION:

Our data demonstrate a novel role of IL-10 in regulation of pathological autophagy; thus can act as a potential therapeutic molecule for treatment of chronic heart disease.

KEYWORDS:

Autophagy; Cardiomyocytes; PI3K/Akt signaling; Signaling; mTORC1

PMID:
26549357
PMCID:
PMC4689660
DOI:
10.1016/j.yjmcc.2015.11.004
[Indexed for MEDLINE]
Free PMC Article

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