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Lupeol Counteracts the Proinflammatory Signalling Triggered in Macrophages by 7-Keto-Cholesterol: New Perspectives in the Therapy of Atherosclerosis
المؤلفون المشاركون
Togna, Anna Rita
Saha, Sarmistha
Saso, Luciano
Buttari, Brigitta
Riganò, Rachele
Profumo, Elisabetta
المصدر
Oxidative Medicine and Cellular Longevity
العدد
المجلد 2020، العدد 2020 (31 ديسمبر/كانون الأول 2020)، ص ص. 1-12، 12ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2020-09-27
دولة النشر
مصر
عدد الصفحات
12
التخصصات الرئيسية
الملخص EN
Macrophage activation and polarization play a central role in atherosclerotic plaque fate.
The M1/M2 activation phenotypes represent two profiles of the macrophage polarization state.
During atherosclerosis regression or stabilization, macrophages switch from M1 proinflammatory phenotype to M2 anti-inflammatory reparative one.
Here, we investigated whether the natural compound lupeol, a pentacyclic triterpene, induces phenotypical and functional changes in human M1 macrophages and counteracts the proinflammatory signalling triggered by 7-keto-cholesterol (7KC), a major product of oxidative stress-mediated cholesterol oxidation.
Flow cytometric and immunochemical analysis showed that the treatment with lupeol of M1 monocyte-derived macrophages M(IFN-γ/LPS) specifically stimulated these cells to upregulate the expression of the anti-inflammatory cytokines interleukin- (IL-)10 and TGF-β, and of the scavenger receptor CD36, whereas downregulated the proinflammatory cytokine IL-12 and the M1 activation marker HLA-DR.
Pretreatment of macrophages with lupeol prevented the release of IL-12, IL-1β, and the upregulation of HLA-DR expression triggered by 7KC and increased the IL-10 production and CD36 expression.
This treatment also prevented the impairment of endocytosis triggered by 7KC and prevented 7KC-induced foam cell formation by reducing the lipid droplet accumulation in M1-polarized THP-1 macrophages, whereas showed an additive effect in reactive oxygen species (ROS) production.
Western blotting analysis of autophagy markers LC3-I/II and p62-SQSTM1 in M1-polarized THP-1 macrophages demonstrated that lupeol activated autophagy as indicated by increased LC3-II levels, and by marked inhibition of p62.
These findings indicate that lupeol has a cytoprotective effect on 7KC-proinflammatory signalling by efficiently switching the macrophage polarization toward an anti-inflammatory phenotype, probably through the activation of the autophagy pathway by increasing ROS production, the reduction of cellular lipid accumulation, and an overall reduction of proinflammatory phenotype.
Thus, our data demonstrating an anti-inflammatory and immunomodulatory activity of lupeol in human M1 macrophages suggest its usefulness as an adjunctive drug in the therapy of atherosclerosis.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Saha, Sarmistha& Profumo, Elisabetta& Togna, Anna Rita& Riganò, Rachele& Saso, Luciano& Buttari, Brigitta. 2020. Lupeol Counteracts the Proinflammatory Signalling Triggered in Macrophages by 7-Keto-Cholesterol: New Perspectives in the Therapy of Atherosclerosis. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-12.
https://search.emarefa.net/detail/BIM-1203638
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Saha, Sarmistha…[et al.]. Lupeol Counteracts the Proinflammatory Signalling Triggered in Macrophages by 7-Keto-Cholesterol: New Perspectives in the Therapy of Atherosclerosis. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-12.
https://search.emarefa.net/detail/BIM-1203638
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Saha, Sarmistha& Profumo, Elisabetta& Togna, Anna Rita& Riganò, Rachele& Saso, Luciano& Buttari, Brigitta. Lupeol Counteracts the Proinflammatory Signalling Triggered in Macrophages by 7-Keto-Cholesterol: New Perspectives in the Therapy of Atherosclerosis. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-12.
https://search.emarefa.net/detail/BIM-1203638
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1203638
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
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