Lipopolysaccharides improve mesenchymal stem cell-mediated cardioprotection by MyD88 and stat3 signaling in a mouse model of cardiac ischemia/reperfusion injury

Xiaona Chu, Bing Xu, Hongyu Gao, Bai Yan Li, Yunlong Liu, Jill Reiter, Yue Wang

Research output: Contribution to journalArticle

Abstract

Bone marrow-derived mesenchymal stem cells (MSCs) improve cardiac function after ischemia/reperfusion injury, in part, due to the release of cytoprotective paracrine factors. Toll-like receptor 4 (TLR4) is expressed in MSCs and regulates the expression of cytoprotective factors, cytokines, and chemokines. Lipopolysaccharide (LPS) stimulation of TLR4 activates two distinct signaling pathways that are either MyD88 dependent or MyD88 independent/TIR-domain-containing adapter-inducing interferon-β (TRIF) dependent. While it was reported previously that LPS treatment improved MSC-mediated cardioprotection, the mechanism underlying such improved effect remains unknown. To study the role of MyD88 signaling in MSC cardioprotective activity, wild type (WT) and MyD88 -/- MSCs were treated with LPS (200 ng/mL) for 24 h. WT and MyD88 -/- MSCs with or without LPS pretreatment were infused into the coronary circulation of isolated mouse hearts (Langendorff model) and then subjected to ischemia (25 min) and reperfusion (50 min). Saline served as a negative control. Both untreated and LPS-pretreated WT MSCs significantly improved postischemic recovery of myocardial function of isolated mouse hearts, as evidenced by improved left ventricular developed pressure and ventricular contractility assessment (ie, the rate of left ventricle pressure change over time, ± dp/dt). LPS-pretreated WT MSCs conferred better cardiac function recovery than untreated MSCs; however, such effect of LPS was abolished when using MyD88 -/- MSCs. In addition, LPS stimulated stat3 activity in WT MSCs, but not MyD88 -/- MSCs. stat3 small interfering RNA abolished the effect of LPS in improving the cardioprotection of WT MSCs. In conclusion, this study demonstrates that LPS improves MSC-mediated cardioprotection by MyD88-dependent activation of stat3.

Original languageEnglish (US)
Pages (from-to)620-631
Number of pages12
JournalStem Cells and Development
Volume28
Issue number9
DOIs
StatePublished - May 1 2019

Fingerprint

Reperfusion Injury
Mesenchymal Stromal Cells
Lipopolysaccharides
Toll-Like Receptor 4
Recovery of Function
Coronary Circulation
Ventricular Pressure
Chemokines
Interferons
Small Interfering RNA
Reperfusion
Heart Ventricles
Ischemia
Bone Marrow

Keywords

  • ischemia/reperfusion
  • LPS
  • MSC
  • paracrine factors
  • stat3
  • TLR4

ASJC Scopus subject areas

  • Hematology
  • Developmental Biology
  • Cell Biology

Cite this

@article{573cd31ae3dc453d839f6f71e4196459,
title = "Lipopolysaccharides improve mesenchymal stem cell-mediated cardioprotection by MyD88 and stat3 signaling in a mouse model of cardiac ischemia/reperfusion injury",
abstract = "Bone marrow-derived mesenchymal stem cells (MSCs) improve cardiac function after ischemia/reperfusion injury, in part, due to the release of cytoprotective paracrine factors. Toll-like receptor 4 (TLR4) is expressed in MSCs and regulates the expression of cytoprotective factors, cytokines, and chemokines. Lipopolysaccharide (LPS) stimulation of TLR4 activates two distinct signaling pathways that are either MyD88 dependent or MyD88 independent/TIR-domain-containing adapter-inducing interferon-β (TRIF) dependent. While it was reported previously that LPS treatment improved MSC-mediated cardioprotection, the mechanism underlying such improved effect remains unknown. To study the role of MyD88 signaling in MSC cardioprotective activity, wild type (WT) and MyD88 -/- MSCs were treated with LPS (200 ng/mL) for 24 h. WT and MyD88 -/- MSCs with or without LPS pretreatment were infused into the coronary circulation of isolated mouse hearts (Langendorff model) and then subjected to ischemia (25 min) and reperfusion (50 min). Saline served as a negative control. Both untreated and LPS-pretreated WT MSCs significantly improved postischemic recovery of myocardial function of isolated mouse hearts, as evidenced by improved left ventricular developed pressure and ventricular contractility assessment (ie, the rate of left ventricle pressure change over time, ± dp/dt). LPS-pretreated WT MSCs conferred better cardiac function recovery than untreated MSCs; however, such effect of LPS was abolished when using MyD88 -/- MSCs. In addition, LPS stimulated stat3 activity in WT MSCs, but not MyD88 -/- MSCs. stat3 small interfering RNA abolished the effect of LPS in improving the cardioprotection of WT MSCs. In conclusion, this study demonstrates that LPS improves MSC-mediated cardioprotection by MyD88-dependent activation of stat3.",
keywords = "ischemia/reperfusion, LPS, MSC, paracrine factors, stat3, TLR4",
author = "Xiaona Chu and Bing Xu and Hongyu Gao and Li, {Bai Yan} and Yunlong Liu and Jill Reiter and Yue Wang",
year = "2019",
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language = "English (US)",
volume = "28",
pages = "620--631",
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TY - JOUR

T1 - Lipopolysaccharides improve mesenchymal stem cell-mediated cardioprotection by MyD88 and stat3 signaling in a mouse model of cardiac ischemia/reperfusion injury

AU - Chu, Xiaona

AU - Xu, Bing

AU - Gao, Hongyu

AU - Li, Bai Yan

AU - Liu, Yunlong

AU - Reiter, Jill

AU - Wang, Yue

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Bone marrow-derived mesenchymal stem cells (MSCs) improve cardiac function after ischemia/reperfusion injury, in part, due to the release of cytoprotective paracrine factors. Toll-like receptor 4 (TLR4) is expressed in MSCs and regulates the expression of cytoprotective factors, cytokines, and chemokines. Lipopolysaccharide (LPS) stimulation of TLR4 activates two distinct signaling pathways that are either MyD88 dependent or MyD88 independent/TIR-domain-containing adapter-inducing interferon-β (TRIF) dependent. While it was reported previously that LPS treatment improved MSC-mediated cardioprotection, the mechanism underlying such improved effect remains unknown. To study the role of MyD88 signaling in MSC cardioprotective activity, wild type (WT) and MyD88 -/- MSCs were treated with LPS (200 ng/mL) for 24 h. WT and MyD88 -/- MSCs with or without LPS pretreatment were infused into the coronary circulation of isolated mouse hearts (Langendorff model) and then subjected to ischemia (25 min) and reperfusion (50 min). Saline served as a negative control. Both untreated and LPS-pretreated WT MSCs significantly improved postischemic recovery of myocardial function of isolated mouse hearts, as evidenced by improved left ventricular developed pressure and ventricular contractility assessment (ie, the rate of left ventricle pressure change over time, ± dp/dt). LPS-pretreated WT MSCs conferred better cardiac function recovery than untreated MSCs; however, such effect of LPS was abolished when using MyD88 -/- MSCs. In addition, LPS stimulated stat3 activity in WT MSCs, but not MyD88 -/- MSCs. stat3 small interfering RNA abolished the effect of LPS in improving the cardioprotection of WT MSCs. In conclusion, this study demonstrates that LPS improves MSC-mediated cardioprotection by MyD88-dependent activation of stat3.

AB - Bone marrow-derived mesenchymal stem cells (MSCs) improve cardiac function after ischemia/reperfusion injury, in part, due to the release of cytoprotective paracrine factors. Toll-like receptor 4 (TLR4) is expressed in MSCs and regulates the expression of cytoprotective factors, cytokines, and chemokines. Lipopolysaccharide (LPS) stimulation of TLR4 activates two distinct signaling pathways that are either MyD88 dependent or MyD88 independent/TIR-domain-containing adapter-inducing interferon-β (TRIF) dependent. While it was reported previously that LPS treatment improved MSC-mediated cardioprotection, the mechanism underlying such improved effect remains unknown. To study the role of MyD88 signaling in MSC cardioprotective activity, wild type (WT) and MyD88 -/- MSCs were treated with LPS (200 ng/mL) for 24 h. WT and MyD88 -/- MSCs with or without LPS pretreatment were infused into the coronary circulation of isolated mouse hearts (Langendorff model) and then subjected to ischemia (25 min) and reperfusion (50 min). Saline served as a negative control. Both untreated and LPS-pretreated WT MSCs significantly improved postischemic recovery of myocardial function of isolated mouse hearts, as evidenced by improved left ventricular developed pressure and ventricular contractility assessment (ie, the rate of left ventricle pressure change over time, ± dp/dt). LPS-pretreated WT MSCs conferred better cardiac function recovery than untreated MSCs; however, such effect of LPS was abolished when using MyD88 -/- MSCs. In addition, LPS stimulated stat3 activity in WT MSCs, but not MyD88 -/- MSCs. stat3 small interfering RNA abolished the effect of LPS in improving the cardioprotection of WT MSCs. In conclusion, this study demonstrates that LPS improves MSC-mediated cardioprotection by MyD88-dependent activation of stat3.

KW - ischemia/reperfusion

KW - LPS

KW - MSC

KW - paracrine factors

KW - stat3

KW - TLR4

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U2 - 10.1089/scd.2018.0213

DO - 10.1089/scd.2018.0213

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SN - 1547-3287

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