Lipopolysaccharides induced inflammatory responses and electrophysiological dysfunctions in human-induced pluripotent stem cell derived cardiomyocytes

Abstract Severe infections like sepsis lead frequently to cardiomyopathy. The mechanisms are unclear and an optimal therapy for septic cardiomyopathy still lacks. The aim of this study is to establish an endotoxin-induced inflammatory model using human induced pluripotent stem cell (hiPSC) derived c...

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Autores principales:	Gökhan Yücel, Zhihan Zhao, Ibrahim El-Battrawy, Huan Lan, Siegfried Lang, Xin Li, Fanis Buljubasic, Wolfram-Hubertus Zimmermann, Lukas Cyganek, Jochen Utikal, Ursula Ravens, Thomas Wieland, Martin Borggrefe, Xiao-Bo Zhou, Ibrahim Akin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cdc733ed36b44e63821868b53911c08a
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spelling	oai:doaj.org-article:cdc733ed36b44e63821868b53911c08a2021-12-02T15:05:12ZLipopolysaccharides induced inflammatory responses and electrophysiological dysfunctions in human-induced pluripotent stem cell derived cardiomyocytes10.1038/s41598-017-03147-42045-2322https://doaj.org/article/cdc733ed36b44e63821868b53911c08a2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03147-4https://doaj.org/toc/2045-2322Abstract Severe infections like sepsis lead frequently to cardiomyopathy. The mechanisms are unclear and an optimal therapy for septic cardiomyopathy still lacks. The aim of this study is to establish an endotoxin-induced inflammatory model using human induced pluripotent stem cell (hiPSC) derived cardiomyocytes (hiPSC-CMs) for mechanistic and therapeutic studies. hiPSC-CMs were treated by lipopolysaccharide (LPS) in different concentrations for different times. ELISA, FACS, qPCR, and patch-clamp techniques were used for the study. TLR4 (Toll-like receptor 4) and its associated proteins, CD14, LBP (lipopolysaccharide binding protein), TIRAP (toll-interleukin 1 receptor domain containing adaptor protein), Ly96 (lymphocyte antigen 96) and nuclear factor kappa B as well as some pro-and anti-inflammatory factors are expressed in hiPSC-CMs. LPS-treatment for 6 hours increased the expression levels of pro-inflammatory and chemotactic cytokines (TNF-a, IL-1ß, IL-6, CCL2, CCL5, IL-8), whereas 48 hour-treatment elevated the expression of anti-inflammatory factors (IL-10 and IL-6). LPS led to cell injury resulting from exaggerated cell apoptosis and necrosis. Finally, LPS inhibited small conductance Ca2+-activated K+ channel currents, enhanced Na+/Ca2+-exchanger currents, prolonged action potential duration, suggesting cellular electrical dysfunctions. Our data demonstrate that hiPSC-CMs possess the functional reaction system involved in endotoxin-induced inflammation and can model some bacterium-induced inflammatory responses in cardiac myocytes.Gökhan YücelZhihan ZhaoIbrahim El-BattrawyHuan LanSiegfried LangXin LiFanis BuljubasicWolfram-Hubertus ZimmermannLukas CyganekJochen UtikalUrsula RavensThomas WielandMartin BorggrefeXiao-Bo ZhouIbrahim AkinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gökhan Yücel Zhihan Zhao Ibrahim El-Battrawy Huan Lan Siegfried Lang Xin Li Fanis Buljubasic Wolfram-Hubertus Zimmermann Lukas Cyganek Jochen Utikal Ursula Ravens Thomas Wieland Martin Borggrefe Xiao-Bo Zhou Ibrahim Akin Lipopolysaccharides induced inflammatory responses and electrophysiological dysfunctions in human-induced pluripotent stem cell derived cardiomyocytes
description	Abstract Severe infections like sepsis lead frequently to cardiomyopathy. The mechanisms are unclear and an optimal therapy for septic cardiomyopathy still lacks. The aim of this study is to establish an endotoxin-induced inflammatory model using human induced pluripotent stem cell (hiPSC) derived cardiomyocytes (hiPSC-CMs) for mechanistic and therapeutic studies. hiPSC-CMs were treated by lipopolysaccharide (LPS) in different concentrations for different times. ELISA, FACS, qPCR, and patch-clamp techniques were used for the study. TLR4 (Toll-like receptor 4) and its associated proteins, CD14, LBP (lipopolysaccharide binding protein), TIRAP (toll-interleukin 1 receptor domain containing adaptor protein), Ly96 (lymphocyte antigen 96) and nuclear factor kappa B as well as some pro-and anti-inflammatory factors are expressed in hiPSC-CMs. LPS-treatment for 6 hours increased the expression levels of pro-inflammatory and chemotactic cytokines (TNF-a, IL-1ß, IL-6, CCL2, CCL5, IL-8), whereas 48 hour-treatment elevated the expression of anti-inflammatory factors (IL-10 and IL-6). LPS led to cell injury resulting from exaggerated cell apoptosis and necrosis. Finally, LPS inhibited small conductance Ca2+-activated K+ channel currents, enhanced Na+/Ca2+-exchanger currents, prolonged action potential duration, suggesting cellular electrical dysfunctions. Our data demonstrate that hiPSC-CMs possess the functional reaction system involved in endotoxin-induced inflammation and can model some bacterium-induced inflammatory responses in cardiac myocytes.
format	article
author	Gökhan Yücel Zhihan Zhao Ibrahim El-Battrawy Huan Lan Siegfried Lang Xin Li Fanis Buljubasic Wolfram-Hubertus Zimmermann Lukas Cyganek Jochen Utikal Ursula Ravens Thomas Wieland Martin Borggrefe Xiao-Bo Zhou Ibrahim Akin
author_facet	Gökhan Yücel Zhihan Zhao Ibrahim El-Battrawy Huan Lan Siegfried Lang Xin Li Fanis Buljubasic Wolfram-Hubertus Zimmermann Lukas Cyganek Jochen Utikal Ursula Ravens Thomas Wieland Martin Borggrefe Xiao-Bo Zhou Ibrahim Akin
author_sort	Gökhan Yücel
title	Lipopolysaccharides induced inflammatory responses and electrophysiological dysfunctions in human-induced pluripotent stem cell derived cardiomyocytes
title_short	Lipopolysaccharides induced inflammatory responses and electrophysiological dysfunctions in human-induced pluripotent stem cell derived cardiomyocytes
title_full	Lipopolysaccharides induced inflammatory responses and electrophysiological dysfunctions in human-induced pluripotent stem cell derived cardiomyocytes
title_fullStr	Lipopolysaccharides induced inflammatory responses and electrophysiological dysfunctions in human-induced pluripotent stem cell derived cardiomyocytes
title_full_unstemmed	Lipopolysaccharides induced inflammatory responses and electrophysiological dysfunctions in human-induced pluripotent stem cell derived cardiomyocytes
title_sort	lipopolysaccharides induced inflammatory responses and electrophysiological dysfunctions in human-induced pluripotent stem cell derived cardiomyocytes
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/cdc733ed36b44e63821868b53911c08a
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Lipopolysaccharides induced inflammatory responses and electrophysiological dysfunctions in human-induced pluripotent stem cell derived cardiomyocytes

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