Stimulation of P2Y11 receptor modulates cardiac fibroblasts secretome toward immunomodulatory and protective roles after Hypoxia/Reoxygenation injury
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
References
Citations
Related Concepts
Related Feeds
Biomarkers for Cardiovascular Risk Assessment
Sensitive and accurate biomarkers used in cardiovascular risk prediction can potentially be used to manage the risk of cardiovascular disease. Discover the latest research on Biomarkers for Cardiovascular Risk Assessment here. Discover the latest research on Biomarkers for Cardiovascular Risk Assessment here.