1-Methylnicotinamide (1-MNA) inhibits the activation of the NLRP3 inflammasome in human macrophages.

Autor: Sidor K; Department of Translational Immunology and Experimental Intensive Care, Centre of Postgraduate Medical Education, Warsaw, Poland., Jeznach A; Department of Translational Immunology and Experimental Intensive Care, Centre of Postgraduate Medical Education, Warsaw, Poland., Hoser G; Department of Translational Immunology and Experimental Intensive Care, Centre of Postgraduate Medical Education, Warsaw, Poland., Skirecki T; Department of Translational Immunology and Experimental Intensive Care, Centre of Postgraduate Medical Education, Warsaw, Poland. Electronic address: tskirecki@cmkp.edu.pl.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2023 Aug; Vol. 121, pp. 110445. Date of Electronic Publication: 2023 Jun 06.
DOI: 10.1016/j.intimp.2023.110445
Abstrakt: The NLRP3 inflammasome is among the most potent intracellular sensors of danger and disturbances of cellular homeostasis that can lead to the release of IL-1β and cell death, or pyroptosis. Despite its protective role, this mechanism is involved in the pathogenesis of numerous inflammatory diseases; therefore, it is seen as a potential therapeutic target. 1-methylnicotinamide (1-MNA) is a direct metabolite of nicotinamide and was previously shown to display several immunomodulatory properties, including a reduction in the reactive oxygen species (ROS). Here, we investigated whether 1-MNA could influence the activation of the NLRP3 inflammasome in human macrophages. In differentiated human macrophages we observed that 1-MNA specifically reduced the activation of the NLRP3 inflammasome. This effect was related to the scavenging of ROS, as exogenous H 2 O 2 was able to restore NLRP3 activation. Additionally, 1-MNA increased the mitochondrial membrane potential, indicating that it did not inhibit oxidative phosphorylation. Moreover, at high but not low concentrations, 1-MNA decreased NF-κB activation and the level of pro-IL-1β. Interestingly, 1-MNA did not reduce the secretion of IL-6 upon endotoxin stimulation, confirming that its primary immunomodulatory effect on human macrophages is dependent on the NLRP3 inflammasome. Taken together, we have shown for the first time that 1-MNA reduced the activation of the NLRP3 inflammasome in human macrophages via an ROS-dependent pathway. Our results indicate a novel potential use of 1-MNA in NLRP3-related disorders.
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 © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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