ArticleThe Journal of biological chemistry2014
Lysosomes integrate metabolic-inflammatory cross-talk in primary macrophage inflammasome activation.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
90 citing papers in PubMed, 135 citations in OpenAlex.
- Vascular smooth muscle-specific NLRP3 hyperactivation exacerbates arterial intimal hyperplasia in mice.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Dietary Saturated Fatty Acids as Evolutionarily Conserved Signals of Immune Activation.DNA and cell biology · 2026Review
- Galectin-3 mediates lysosome-related inflammation within monocyte-derived macrophages in a mouse model of ischemic brain injury.The Journal of clinical investigation · 2026Article
- Intracellular Calcium as a Regulator of Polarization and Target Reprogramming of Macrophages.International journal of molecular sciences · 2025Review
- Inflammasome Signaling in Cardiac Arrhythmias: Linking Inflammation, Fibrosis, and Electrical Remodeling.International journal of molecular sciences · 2025Review
- sPLA2-IIA modifies progranulin deficiency phenotypes in mouse models.Molecular neurodegeneration · 2025Article
- Estimation of fatty acid composition in mammary adipose tissue using deep neural network with unsupervised training.Magnetic resonance in medicine · 2025Article
- Inflammasome Activation and Neutrophil Extracellular Traps in Atherosclerosis.Journal of atherosclerosis and thrombosis · 2025Review
- Review
- Review
- Leveraging a comprehensive unbiased RNAseq database to characterize human monocyte-derived macrophage gene expression profiles within commonly employed in vitro polarization methods.Scientific reports · 2024Article
- Lysosomal physiology and pancreatic lysosomal stress in diabetes mellitus.eGastroenterology · 2024Article
- ER-to-lysosome CaeLife · 2024Article
- Review
- NLRP inflammasomes in health and disease.Molecular biomedicine · 2024Review
- MSCs alleviate LPS-induced acute lung injury by inhibiting the proinflammatory function of macrophages in mouse lung organoid-macrophage model.Cellular and molecular life sciences : CMLS · 2024Article
- Lysosomal BK channels facilitate silica-induced inflammation in macrophages.Inhalation toxicology · 2024Article
- Potential Impact of Bioactive Compounds as NLRP3 Inflammasome Inhibitors: An Update.Current pharmaceutical biotechnology · 2024Review
- The NLRP3 inflammasome in ischemic stroke.Frontiers in stroke · 2024Review
- Protective Effect of Topiramate against Diabetic Retinopathy and Computational Approach Recognizing the Role of NLRP3/IL-1β/TNF-α Signaling.Biomedicines · 2023Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Macrophage dysfunction and inflammasome activation have been implicated in the pathogenesis of diabetes and its complications. Prolonged inflammation and impaired healing are hallmarks of the diabetic response to tissue injury, and excessive inflammasome activation has been associated in these phenotypes. However, the mechanisms that regulate the inflammasome in response to lipid metabolic and inflammatory stress are incompletely understood. We have shown previously that IL-1β secretion is induced in primary macrophages exposed to the dietary saturated fatty acid palmitate in combination with LPS. In this study, we sought to unravel the mechanisms underlying the activation of this lipotoxic inflammasome. We demonstrate that palmitate-loaded primary macrophages challenged with LPS activate the NLRP3 inflammasome through a mechanism that involves the lysosome. Interestingly, the lysosome was involved in both the regulation of pro-IL-1β levels and its subsequent cleavage/release. The lysosomal protease cathepsin B was required for IL-1β release but not pro-IL-1β production. In contrast, disrupting lysosomal calcium regulation decreased IL-1β release by reducing pro-IL-1β levels. The calcium pathway involved the calcium-activated phosphatase calcineurin, which stabilized IL-1β mRNA. Our findings provide evidence that the lysosome plays a key role in both the priming and assembly phases of the lipostoxic inflammasome. These findings have potential relevance to the hyperinflammatory phenotypes observed in diabetics during tissue damage or infection and identify lysosomes and calcineurin as potential therapeutic targets.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.