Flagellin-Induced Immune Response in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes

被引：2

作者：

Yuecel, Goekhan ^{[1
,2
,3
,11
]}

Zhou, Xiaobo ^{[1
,2
,3
]}

Terkatz, Linda ^{[1
,4
]}

Wendel, Angela ^{[1
,2
,3
]}

Reinhardt, Julius ^{[1
,2
,3
]}

El-Battrawy, Ibrahim ^{[5
]}

Sattler, Katherine ^{[1
,2
,3
]}

Cyganek, Lukas ^{[6
,7
]}

Utikal, Jochen ^{[8
,9
,10
]}

Langer, Harald ^{[1
,2
,3
]}

Scharf, Ruediger ^{[1
,2
,3
]}

Duerschmied, Daniel ^{[1
,2
,3
]}

Akin, Ibrahim ^{[1
,2
,3
]}

机构：

[1] Heidelberg Univ, Univ Med Ctr Mannheim, Med Fac Mannheim, Dept Cardiol Angiol Haemostaseol & Med Intens Care, D-68167 Mannheim, Germany

[2] European Ctr AngioSci ECAS, D-68167 Mannheim, Germany

[3] German Ctr Cardiovasc Res DZHK Partner Site Heidel, D-68167 Mannheim, Germany

[4] Childrens Hosp Cologne, Dept Pediat Surg & Pediat Urol, D-50735 Cologne, Germany

[5] Ruhr Univ Bochum, Bergmannsheil Univ Hosp, Dept Cardiol & Angiol, D-44791 Bochum, Germany

[6] DZHK German Ctr Cardiovasc Res, Partner Site, D-37075 Gottingen, Germany

[7] Univ Med Ctr Goettingen, Stem Cell Unit, Clin Cardiol & Pneumol, D-37075 Gottingen, Germany

[8] German Canc Res Ctr, Skin Canc Unit, D-69120 Heidelberg, Germany

[9] Heidelberg Univ, Dept Dermatol Venereol & Allergol, D-68167 Mannheim, Germany

[10] Heidelberg Univ, Univ Med Ctr Mannheim, DKFZ Hector Canc Inst, D-68167 Mannheim, Germany

[11] Univ Med Ctr Mannheim, Dept Med 1, Theodor Kutzer Ufer 1 3, D-68167 Mannheim, Germany

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2023年 / 24卷 / 18期

关键词：

hiPSC-CM; PAMP; TLR; innate immunity; septic cardiomyopathy; TOLL-LIKE RECEPTORS; LIPOTEICHOIC ACID; STAPHYLOCOCCUS-AUREUS; CARDIAC MYOCYTES; INNATE; CONTRACTILITY; INFLAMMATION; ACTIVATION; INDUCTION; MATURATION;

D O I：

10.3390/ijms241813933

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Pathogen-associated molecular patterns (PAMPs) are involved in the pathogenesis of septic cardiomyopathy through a toll-like receptor (TLR)-mediated immune response. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) can reflect the innate immune abilities of cardiomyocytes. Therefore, hiPSC-CMs may provide an attractive tool with which to study PAMP-induced alterations in cardiomyocytes. HiPSC-CMs from two different healthy donors were exposed to the PAMP flagellin (FLA) at different doses and exposure times. Alterations in the expression levels of distinct inflammation-associated cytokines, intracellular inflammation pathways including TLR5 downstream signaling, reactive oxygen species levels and surface antigen composition were assessed using PCR, ELISA and FACS techniques. Higher doses of flagellin increased the expression levels of inflammation-associated cytokines like TNFa (p < 0.01) and downstream signaling molecules like caspase-8 (p < 0.05). TLR5 expression (p < 0.01) and TLR5 fluorescence proportion (p < 0.05) increased in hiPSC-CMs after prolonged FLA exposure. FLA-induced innate immune response processes in cardiomyocytes might be detectable with an hiPSC-CMs-based in vitro model.

引用

页数：13

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[1] DIFFERENTIATION WITHIN BACTERIAL FLAGELLUM AND ISOLATION OF PROXIMAL HOOK [J].