Carvedilol attenuates inflammatory reactions of lipopolysaccharide-stimulated BV2 cells and modulates M1/M2 polarization of microglia via regulating NLRP3, Notch, and PPAR-γ signaling pathways.

التفاصيل البيبلوغرافية
العنوان:	Carvedilol attenuates inflammatory reactions of lipopolysaccharide-stimulated BV2 cells and modulates M1/M2 polarization of microglia via regulating NLRP3, Notch, and PPAR-γ signaling pathways.
المؤلفون:	Khoshnavay Foumani M; Research Laboratory for Embryology and Stem Cells, Department of Anatomical Sciences, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran., Amirshahrokhi K; Department of Pharmacology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran., Namjoo Z; Research Laboratory for Embryology and Stem Cells, Department of Anatomical Sciences, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran. znamjoo1392@gmail.com., Niapour A; Research Laboratory for Embryology and Stem Cells, Department of Anatomical Sciences, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran. a.niapour@arums.ac.ir.
المصدر:	Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2024 Jul; Vol. 397 (7), pp. 4727-4736. Date of Electronic Publication: 2023 Dec 22.
نوع المنشور:	Journal Article
اللغة:	English
بيانات الدورية:	Publisher: Springer Verlag Country of Publication: Germany NLM ID: 0326264 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1912 (Electronic) Linking ISSN: 00281298 NLM ISO Abbreviation: Naunyn Schmiedebergs Arch Pharmacol Subsets: MEDLINE
أسماء مطبوعة:	Original Publication: Berlin, New York, Springer Verlag.
مواضيع طبية MeSH:	Microglia/drug effects , Microglia/metabolism , Lipopolysaccharides* , PPAR gamma/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Signal Transduction/drug effects , Carvedilol/pharmacology , Anti-Inflammatory Agents/pharmacology , Reactive Oxygen Species/metabolism, Animals ; Mice ; Humans ; Cell Line ; Cell Survival/drug effects ; Inflammation/drug therapy ; Inflammation/metabolism ; Inflammation/pathology ; Interleukin-1beta/metabolism ; Cell Line, Tumor ; Receptor, Notch1/metabolism
مستخلص:	Microglial cells coordinate immune responses in the central nervous system. Carvedilol (CVL) is a non-selective β-blocker with anti-inflammatory and anti-oxidant effects. This study aims to investigate the anti-inflammatory effects and the underlying mechanisms of CVL on lipopolysaccharide (LPS)-induced inflammation in microglial BV2 cells. BV2 cells were stimulated with LPS, and the protective effects of CVL were investigated via measurement of cell viability, reactive oxygen species (ROS), and interleukin (IL)-1β liberation. The protein levels of some inflammatory cascade, Notch, and peroxisome proliferator-activated receptor (PPAR)-γ pathways and relative markers of M1/M2 microglial phenotypes were assessed. Neuroblastoma SH-SY5Y cells were cultured with a BV2-conditioned medium (CM), and the capacity of CVL to protect cell viability was evaluated. CVL displayed a protective effect against LPS stress through reducing ROS and down-regulating of nuclear factor kappa B (NF-κB) p65, NLR family pyrin domain containing-3 (NLRP3), and IL-1β proteins. LPS treatment significantly increased the levels of the M1 microglial marker inducible nitric oxide synthase (iNOS) and M1-associated cleaved-NOTCH1 and hairy and enhancer of split-1 (HES1) proteins. Conversely, LPS treatment reduced the levels of the M2 marker arginase-1 (Arg-1) and PPAR-γ proteins. CVL pre-treatment reduced the protein levels of iNOS, cleaved-NOTCH1, and HES1, while increased Arg-1 and PPAR-γ. CM of CVL-primed BV2 cells significantly improved SH-SY5Y cell viability as compared with the LPS-induced cells. CVL suppressed ROS production and alleviated the expression of inflammatory markers in LPS-stimulated BV2 cells. Our results demonstrated that targeting Notch and PPAR-γ pathways as well as directing BV2 cell polarization toward the M2 phenotype may provide a therapeutic strategy to suppress neuroinflammation by CVL. (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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معلومات مُعتمدة:	IR.ARUMS.REC.1400.203 Ardabil University of Medical Sciences
فهرسة مساهمة:	Keywords: Carvedilol; Microglial polarization; NLRP3 inflammasome; Neuroinflammation; Notch signaling
المشرفين على المادة:	0 (Lipopolysaccharides) 0 (PPAR gamma) 0 (NLR Family, Pyrin Domain-Containing 3 Protein) 0K47UL67F2 (Carvedilol) 0 (Anti-Inflammatory Agents) 0 (Reactive Oxygen Species) 0 (Nlrp3 protein, mouse) 0 (Interleukin-1beta) 0 (Receptor, Notch1)
تواريخ الأحداث:	Date Created: 20231222 Date Completed: 20240611 Latest Revision: 20240611
رمز التحديث:	20240611
DOI:	10.1007/s00210-023-02914-7
PMID:	38133658
قاعدة البيانات:	MEDLINE

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تدمد:	1432-1912
DOI:	10.1007/s00210-023-02914-7