TY  - JOUR
AU  - Sattler, Katherine
AU  - El-Battrawy, Ibrahim
AU  - Cyganek, Lukas
AU  - Lang, Siegfried
AU  - Lan, Huan
AU  - Li, Xin
AU  - Zhao, Zhihan
AU  - Utikal, Jochen
AU  - Wieland, Thomas
AU  - Borggrefe, Martin
AU  - Zhou, Xiaobo
AU  - Akin, Ibrahim
TI  - TRPV1 activation and internalization is part of the LPS-induced inflammation in human iPSC-derived cardiomyocytes.
JO  - Scientific reports
VL  - 11
IS  - 1
SN  - 2045-2322
CY  - [London]
PB  - Macmillan Publishers Limited, part of Springer Nature
M1  - DKFZ-2021-01631
SP  - 14689
PY  - 2021
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:34282193
DO  - DOI:10.1038/s41598-021-93958-3
UR  - https://inrepo02.dkfz.de/record/169897
ER  -