Inhibitory effects of lovastatin on inflammatory cytokines and NLRP3 inflammasome activation in human macrophages 2526
Year: 2025
Type: article
Abstract: Description Environmental pollutants such as particulate matter and endotoxin are strong inducers of respiratory inflammation. While macrophages are crucial for immune defense, their overactivation can trigger cytokine storms and organ failure. Statins have shown promise in modulating excessive immune responses, reducing cytokine production, and enhancing bacterial clearance. Lovastatin is known to alleviate oxidative stress and inflammation by inhibiting NO, iNOS, and TNF-α via STAT1 and mTOR pathways. This study investigates the effects of lovastatin on inflammation and NLRP3 inflammasome activity in human macrophages. Our results indicate that lovastatin primarily impacts the initial signaling of the NLRP3 inflammasome by reducing NF-κB translocation, resulting in decreased gene and protein expression of NLRP3. This reduction appears to affect the NLRP3 inflammasome assembly during secondary signaling, thereby inhibiting its activation and caspase-1 cleavage in response to LPS and ATP stimulation. Additionally, lovastatin suppresses pro-IL-1β production, leading to lower IL-1β secretion. Furthermore, under varying LPS stimulation times, lovastatin consistently reduces the gene and protein expression of pro-inflammatory cytokines IL-6, TNF-α, and IL-1β. These findings suggest lovastatin as a potential therapeutic agent for hyperinflammatory conditions, supporting its application in controlling excessive immune activation by targeting cytokine production and inflammasome activity. Topic Categories Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)
Source: The Journal of Immunology
Authors: Zih Han Liao, Ming-Ling Kuo
Institution: Chang Gung University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4416447442
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