TRPV1 activation and internalization is part of the LPS-induced inflammation in human iPSC-derived cardiomyocytes

The non-selective cation channel transient receptor potential vanilloid 1 (TRPV1) is expressed throughout the cardiovascular system. Recent evidence shows a role for TRPV1 in inflammatory processes. The role of TRPV1 for myocardial inflammation has not been established yet. Human induced pluripotent...

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Hauptverfasser: Sattler, Katherine (VerfasserIn) , El-Battrawy, Ibrahim (VerfasserIn) , Cyganek, Lukas (VerfasserIn) , Lang, Siegfried (VerfasserIn) , Lan, Huan (VerfasserIn) , Li, Xin (VerfasserIn) , Zhao, Zhihan (VerfasserIn) , Utikal, Jochen (VerfasserIn) , Wieland, Thomas (VerfasserIn) , Borggrefe, Martin (VerfasserIn) , Zhou, Xiao-Bo (VerfasserIn) , Akın, Ibrahim (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 19 July 2021
In: Scientific reports
Year: 2021, Jahrgang: 11, Pages: 1-12
ISSN:2045-2322
DOI:10.1038/s41598-021-93958-3
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41598-021-93958-3
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41598-021-93958-3
Volltext
Verfasserangaben:Katherine Sattler, Ibrahim El-Battrawy, Lukas Cyganek, Siegfried Lang, Huan Lan, Xin Li, Zhihan Zhao, Jochen Utikal, Thomas Wieland, Martin Borggrefe, Xiaobo Zhou and Ibrahim Akin
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Zusammenfassung:The non-selective cation channel transient receptor potential vanilloid 1 (TRPV1) is expressed throughout the cardiovascular system. Recent evidence shows a role for TRPV1 in inflammatory processes. The role of TRPV1 for myocardial inflammation has not been established yet. Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (hiPSC-CM) from 4 healthy donors were incubated with lipopolysaccharides (LPS, 6 h), TRPV1 agonist capsaicin (CAP, 20 min) or the antagonist capsazepine (CPZ, 20 min). TRPV1 expression was studied by PCR and western blotting. TRPV1 internalization was analyzed by immunofluorescence. Interleukin-6 (IL-6) secretion and phosphorylation of JNK, p38 and ERK were determined by ELISA. TRPV1-associated ion channel current was measured by patch clamp. TRPV1-mRNA and -protein were expressed in hiPSC-CM. TRPV1 was localized in the plasma membrane. LPS significantly increased secretion of IL-6 by 2.3-fold, which was prevented by pre-incubation with CPZ. LPS induced TRPV1 internalization. Phosphorylation levels of ERK, p38 or JNK were not altered by TRPV1 stimulation or inhibition. LPS and IL-6 significantly lowered TRPV1-mediated ion channel current. TRPV1 mediates the LPS-induced inflammation in cardiomyocytes, associated with changes of cellular electrophysiology. LPS-induced inflammation results in TRPV1 internalization. Further studies have to examine the underlying pathways and the clinical relevance of these findings.
Beschreibung:Published: 19 July 2021
Gesehen am 31.05.2022
Beschreibung:Online Resource
ISSN:2045-2322
DOI:10.1038/s41598-021-93958-3