Interleukin-10 inhibits chronic angiotensin II-induced pathological autophagy

Raj Kishore, Prasanna Krishnamurthy, Venkata Naga Srikanth Garikipati, Cindy Benedict, Emily Nickoloff, Mohsin Khan, Jennifer Johnson, Anna M. Gumpert, Walter J. Koch, Suresh Kumar Verma

Research output: Contribution to journalArticle

19 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)203-213
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Volume89
DOIs
StatePublished - Dec 1 2015

Keywords

  • Autophagy
  • Cardiomyocytes
  • MTORC1
  • PI3K/Akt signaling
  • Signaling

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Interleukin-10 inhibits chronic angiotensin II-induced pathological autophagy'. Together they form a unique fingerprint.

Cite this