کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8473146 | 1550384 | 2018 | 34 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Stimulation of P2Y11 receptor modulates cardiac fibroblasts secretome toward immunomodulatory and protective roles after Hypoxia/Reoxygenation injury
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کلمات کلیدی
LPSP2Y purinoceptorHCFCTLH/R - H / RI/R - I / RIschemia reperfusion injury - آسیب مجدد ایسکمیischemia/reperfusion - ایسکمی / رپرفیوژنImmunomodulation - تنظیم ایمنی Cardioprotection - حفاظت از قلبDendritic cells - سلول های دندریتیکCardiac fibroblast - فیبروبلاست قلبcardiac fibroblasts - فیبروبلاست های قلبhuman cardiac fibroblasts - فیبروبلاست های قلب انسانCardiomyocytes - قلب و عروقlipopolysaccharide - لیپوپلی ساکاریدHypoxia - هیپوکسیhypoxia/reoxygenation - هیپوکسیا / اکسیداسیون مجددControl - کنترل
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
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 (â19%) and pro-inflammatory cytokines and ATP secretion (â44% and â83% 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 (â3,8-fold), indicating induction of a tolerogenic profile. Moreover, P2Y11R inhibition in HCF led to high IL-12 secretion in DC, suggesting that the immunomodulatory effect of HCF secretome is P2Y11R-dependant. HCF secretome reduced H/R-induced cardiomyocytes death (â23%) through RISK pathway activation. P2Y11R inhibition in HCF induced a complete loss of HCF secretome protective effect, highlighting the cardioprotective role of P2Y11R. Our data demonstrated paracrine interactions between HCF, cardiomyocytes and DC following H/R, suggesting a key role of HCF in the cellular responses to reperfusion. These results also demonstrated a beneficial role of P2Y11R in HCF during H/R and strongly support the hypothesis that P2Y11R is a modulator of I/R injury.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 121, August 2018, Pages 212-222
Journal: Journal of Molecular and Cellular Cardiology - Volume 121, August 2018, Pages 212-222
نویسندگان
Claudie Lefort, Lauriane Benoist, Stéphanie Chadet, Marie Piollet, Audrey Heraud, Dominique Babuty, Christophe Baron, Fabrice Ivanes, Denis Angoulvant,