IL-10 improves cardiac remodeling after myocardial infarction by stimulating M2 macrophage polarization and fibroblast activation

Mira Jung, Yonggang Ma, Rugmani Padmanabhan Iyer, Kristine Y. DeLeon-Pennell, Andriy Yabluchanskiy, Michael R. Garrett, Merry L. Lindsey

Research output: Contribution to journalArticle

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Abstract

Inflammation resolution is important for scar formation following myocardial infarction (MI) and requires the coordinated actions of macrophages and fibroblasts. In this study, we hypothesized that exogenous interleukin-10 (IL-10), an anti-inflammatory cytokine, promotes post-MI repair through actions on these cardiac cell types. To test this hypothesis, C57BL/6J mice (male, 3- to 6-month old, n = 24/group) were treated with saline or IL-10 (50 μg/kg/day) by osmotic mini-pump infusion starting at day (d) 1 post-MI and sacrificed at d7 post-MI. IL-10 infusion doubled plasma IL-10 concentrations by d7 post-MI. Despite similar infarct areas and mortality rates, IL-10 treatment significantly decreased LV dilation (1.6-fold for end-systolic volume and 1.4-fold for end-diastolic volume) and improved ejection fraction 1.8-fold (both p < 0.05). IL-10 treatment attenuated inflammation at d7 post-MI, evidenced by decreased numbers of Mac-3-positive macrophages in the infarct (p < 0.05). LV macrophages isolated from d7 post-MI mice treated with IL-10 showed significantly elevated gene expression of M2 markers (Arg1, Ym1, and Tgfb1; all p < 0.05). We further performed RNA-seq analysis on post-MI cardiac macrophages and identified 410 significantly different genes (155 increased, 225 decreased by IL-10 treatment). By functional network analysis grouping, the majority of genes (133 out of 410) were part of the cellular assembly and repair functional group. Of these, hyaluronidase 3 (Hyal3) was the most important feature identified by p value. IL-10 treatment decreased Hyal3 by 28%, which reduced hyaluronan degradation and limited collagen deposition (all p < 0.05). In addition, in vivo IL-10 treatment increased fibroblast activation (proliferation, migration, and collagen production), an effect that was both directly and indirectly influenced by macrophage M2 polarization. Combined, our results indicate that in vivo infusion of IL-10 post-MI improves the LV microenvironment to dampen inflammation and facilitate cardiac wound healing.

Original languageEnglish (US)
Article number33
JournalBasic research in cardiology
Volume112
Issue number3
DOIs
StatePublished - May 1 2017

Fingerprint

Interleukin-10
Fibroblasts
Macrophages
Myocardial Infarction
Hyaluronoglucosaminidase
Inflammation
Collagen
Infusion Pumps
Hyaluronic Acid
Inbred C57BL Mouse
Wound Healing
Genes
Cicatrix
Dilatation
Anti-Inflammatory Agents
RNA
Cytokines
Gene Expression
Mortality

Keywords

  • Collagen
  • Fibroblast
  • Hyaluronan
  • IL-10
  • Inflammation
  • Macrophage
  • Myocardial infarction

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

IL-10 improves cardiac remodeling after myocardial infarction by stimulating M2 macrophage polarization and fibroblast activation. / Jung, Mira; Ma, Yonggang; Iyer, Rugmani Padmanabhan; DeLeon-Pennell, Kristine Y.; Yabluchanskiy, Andriy; Garrett, Michael R.; Lindsey, Merry L.

In: Basic research in cardiology, Vol. 112, No. 3, 33, 01.05.2017.

Research output: Contribution to journalArticle

Jung, Mira ; Ma, Yonggang ; Iyer, Rugmani Padmanabhan ; DeLeon-Pennell, Kristine Y. ; Yabluchanskiy, Andriy ; Garrett, Michael R. ; Lindsey, Merry L. / IL-10 improves cardiac remodeling after myocardial infarction by stimulating M2 macrophage polarization and fibroblast activation. In: Basic research in cardiology. 2017 ; Vol. 112, No. 3.
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