Stimulation of P2Y11 receptor modulates cardiac fibroblasts secretome toward immunomodulatory and protective roles after Hypoxia/Reoxygenation injury

Journal of Molecular and Cellular Cardiology
Claudie LefortDenis Angoulvant

Abstract

Cardiac fibroblasts are important regulators of myocardial structure and function. Their implications in pathological processes such as Ischemia/Reperfusion are well characterized. Cardiac fibroblasts respond to stress by excessive proliferation and secretion of pro-inflammatory cytokines and other factors, e.g. ATP, leading to purinergic receptors activation. P2Y11 receptor (P2Y11R) is an ATP-sensitive GPCR playing an immunomodulatory role in human dendritic cells (DC). We hypothesized that P2Y11R stimulation modulated the pro-inflammatory responses of human cardiac fibroblasts (HCF) to Hypoxia/Reoxygenation (H/R) mainly by acting on their secretome. P2Y11R stimulation in HCF at the onset of reoxygenation significantly limited H/R-induced proliferation (-19%) and pro-inflammatory cytokines and ATP secretion (-44% and -83% respectively). Exposure of DC to HCF secretome increased their expression of CD83, CD25 and CD86, suggesting a switch from immature to mature phenotype. Under LPS stimulation, DC had a pro-inflammatory profile (high IL-12/IL-10 ratio) that was decreased by HCF secretome (-3,8-fold), indicating induction of a tolerogenic profile. Moreover, P2Y11R inhibition in HCF led to high IL-12 secretion in DC, suggesting ...Continue Reading

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Citations

Jun 5, 2020·Journal of Receptor and Signal Transduction Research·Daoxin Jin, Fangfang Han
Jun 7, 2019·Journal of Cardiovascular Development and Disease·Kartika R PertiwiEmily Lisa Chilton
Jan 20, 2021·British Journal of Pharmacology·Georg GruenbacherMartin Thurnher
Feb 4, 2019·The Journal of Thoracic and Cardiovascular Surgery·Thierry BourguignonDenis Angoulvant

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