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Published on: July 25, 2022
Protective effects of fatty acid amide hydrolase inhibition in UVB-activated microglia
Veronica Carnicelli1, Noemi De Dominicis2, Lucia Scipioni3
1Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
Abstract:
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.
Insights
Bioactive lipids, specifically fatty acid ethanolamines, can mitigate UVB-induced microglial damage. Inhibiting fatty acid amide hydrolase (FAAH) reduced inflammatory markers and oxidative stress in response to UVB radiation.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Neuroinflammation is central to neurodegenerative diseases, with microglia playing a key role.
- Fatty acid ethanolamines, like anandamide (AEA), are critical regulators of microglial function.
- UVB radiation is a physical stressor that can induce microglial reactivity in the retina and brain.
Purpose of the Study:
- To investigate the impact of fatty acid ethanolamine signaling on microglial responses to UVB radiation.
- To explore the role of fatty acid amide hydrolase (FAAH) in UVB-induced microglial activation.
- To assess the therapeutic potential of FAAH inhibition in mitigating UVB-induced cellular damage.
Main Methods:
- Utilized an in vitro model of mouse microglial BV-2 cells.
- Exposed cells to sub-lethal acute UVB radiation for 24 hours.
- Assessed oxidative stress markers, cyclooxygenase-2 (COX-2) expression, phagocytic and chemotactic activities, and immune profiling.
- Investigated the expression and activity of fatty acid amide hydrolase (FAAH).
- Administered pharmacological FAAH inhibition using URB597.
Main Results:
- UVB exposure increased oxidative stress markers, COX-2 expression, and microglial phagocytic/chemotactic activities.
- UVB radiation selectively upregulated FAAH expression and activity.
- Pharmacological inhibition of FAAH with URB597 counteracted UVB effects.
- FAAH inhibition reduced tumor necrosis factor-α (TNF-α) and nitric oxide (NO) release.
- FAAH inhibition normalized reactive oxidative species (ROS), interleukin-1β (IL-1β), and interleukin-10 (IL-10) levels.
Conclusions:
- Enhanced fatty acid amide signaling shows potential in mitigating UVB-induced cellular damage in microglia.
- FAAH inhibition represents a promising strategy for managing light-induced neuroinflammation.
- Further research into these bioactive lipids could reveal new therapeutic avenues for light-related neurological conditions.
