Protective effects of fatty acid amide hydrolase inhibition in UVB-activated microglia.

Autor: Carnicelli V; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100 L'Aquila, Italy., De Dominicis N; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100 L'Aquila, Italy; Department of Physics, University of Trento, 38123 Trento, Italy., Scipioni L; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100 L'Aquila, Italy; European Center for Brain Research/IRCCS Santa Lucia Foundation, 00143 Rome, Italy., Fava M; Department of Medicine, Campus Bio-Medico University of Rome, 00128 Rome, Italy., Fanti F; Department of Bioscience and Technology for Agriculture, Food and Environment, Campus Universitario di Coste Sant'Agostino, University of Teramo, Italy., Cinque B; Department of Life, Health & Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy., Leuti A; European Center for Brain Research/IRCCS Santa Lucia Foundation, 00143 Rome, Italy; Department of Medicine, Campus Bio-Medico University of Rome, 00128 Rome, Italy., Angelucci CB; Department of Veterinary Medicine, University of Teramo, 64100 Teramo, Italy., Lizzi AR; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100 L'Aquila, Italy., Giacominelli-Stuffler R; Department of Veterinary Medicine, University of Teramo, 64100 Teramo, Italy., Flati V; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100 L'Aquila, Italy., Sergi M; Department of Chemistry, Sapienza University of Rome, Rome, Italy., Compagnone D; Department of Bioscience and Technology for Agriculture, Food and Environment, Campus Universitario di Coste Sant'Agostino, University of Teramo, Italy., Sardanelli AM; Department of Translational Biomedicine and Neuroscience 'DiBraiN', University of Bari 'Aldo Moro', 70121 Bari, Italy., Tisi A; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100 L'Aquila, Italy., Oddi S; European Center for Brain Research/IRCCS Santa Lucia Foundation, 00143 Rome, Italy; Department of Veterinary Medicine, University of Teramo, 64100 Teramo, Italy. Electronic address: soddi@unite.it., Maccarrone M; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100 L'Aquila, Italy; European Center for Brain Research/IRCCS Santa Lucia Foundation, 00143 Rome, Italy. Electronic address: mauro.maccarrone@univaq.it.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular and cell biology of lipids [Biochim Biophys Acta Mol Cell Biol Lipids] 2024 Oct; Vol. 1869 (7), pp. 159524. Date of Electronic Publication: 2024 Jun 08.
DOI: 10.1016/j.bbalip.2024.159524
Abstrakt: Neuroinflammation is a hallmark of several neurodegenerative disorders that has been extensively studied in recent years. Microglia, the primary immune cells of the central nervous system (CNS), are key players in this physiological process, demonstrating a remarkable adaptability in responding to various stimuli in the eye and the brain. Within the complex network of neuroinflammatory signals, the fatty acid N-ethanolamines, in particular N-arachidonylethanolamine (anandamide, AEA), emerged as crucial regulators of microglial activity under both physiological and pathological states. In this study, we interrogated for the first time the impact of the signaling of these bioactive lipids on microglial cell responses to a sub-lethal acute UVB radiation, a physical stressor responsible of microglia reactivity in either the retina or the brain. To this end, we developed an in vitro model using mouse microglial BV-2 cells. Upon 24 h of UVB exposure, BV-2 cells showed elevated oxidative stress markers and, cyclooxygenase (COX-2) expression, enhanced phagocytic and chemotactic activities, along with an altered immune profiling. Notably, UVB exposure led to a selective increase in expression and activity of fatty acid amide hydrolase (FAAH), the main enzyme responsible for degradation of fatty acid ethanolamides. Pharmacological FAAH inhibition via URB597 counteracted the effects of UVB exposure, decreasing tumor necrosis factor α (TNF-α) and nitric oxide (NO) release and reverting reactive oxidative species (ROS), interleukin-1β (IL-1β), and interleukin-10 (IL-10) levels to the control levels. Our findings support the potential of enhanced fatty acid amide signaling in mitigating UVB-induced cellular damage, paving the way to further exploration of these lipids in light-induced immune responses.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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