Trial reportProceedings of the National Academy of Sciences of the United States of America2015
Cell stress increases ATP release in NLRP3 inflammasome-mediated autoinflammatory diseases, resulting in cytokine imbalance.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
64 citing papers in PubMed, 123 citations in OpenAlex.
- Pathogenic NLRP3 mutants form constitutively active inflammasomes resulting in immune-metabolic limitation of IL-1β production.Nature communications · 2024Trial
- Functional Tissue Analysis Reveals Successful Cryopreservation of Human Osteoarthritic Synovium.PloS one · 2016Trial
- Anthracyclines effect on mitochondrial function and biogenesis in normal blood cells of hodgkin lymphoma patients.Scientific reports · 2025Article
- The role of purinergic signaling in acupuncture-mediated relief of neuropathic and inflammatory pain.Purinergic signalling · 2025Review
- NOD1 deficiency promotes inflammation via autophagic degradation of ASK1.Communications biology · 2025Article
- Anti-DAMP therapies for acute inflammation.Frontiers in immunology · 2025Review
- Inflammasome components as new therapeutic targets in inflammatory disease.Nature reviews. Immunology · 2025Review
- Parthenolide ameliorates 3-nitropropionic acid-induced Huntington's disease-like aberrations via modulating NLRP3 inflammasome, reducing microglial activation and inducing astrocyte shifting.Molecular medicine (Cambridge, Mass.) · 2024Article
- Article
- Unexpected chronic lymphocytic leukemia B cell activation by bisphosphonates.Cancer immunology, immunotherapy : CII · 2024Article
- The marine Penicillium sp. GGF16-1-2 metabolite dicitrinone G inhibits pancreatic angiogenesis by regulating the activation of NLRP3 inflammasome.Journal of natural medicines · 2024Article
- Article
- Divergent Oxidative Stress in Normal Tissues and Inflammatory Cells in Hodgkin and Non-Hodgkin Lymphoma.Cancers · 2023Article
- Escalating Bi-Directional Feedback Loops between Proinflammatory Microglia and Mitochondria in Ageing and Post-Diagnosis of Parkinson's Disease.Antioxidants (Basel, Switzerland) · 2023Review
- Article
- Methods to Study NLR in Human Blood Cells.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Tumor intrinsic and extrinsic functions of CD73 and the adenosine pathway in lung cancer.Frontiers in immunology · 2023Review
- The P2YCellular and molecular life sciences : CMLS · 2022Article
- Mitochondrial Generated Redox Stress Differently Affects the Endoplasmic Reticulum of Circulating Lymphocytes and Monocytes in Treatment-Naïve Hodgkin's Lymphoma.Antioxidants (Basel, Switzerland) · 2022Article
- L-plastin enhances NLRP3 inflammasome assembly and bleomycin-induced lung fibrosis.Cell reports · 2022Article
4 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
7 authors at 5 institutions in 3 countries.
Funding
Abstract
Cell stress is implicated in triggering bouts of systemic inflammation in patients with autoinflammatory disorders. Blood monocytes from patients affected by NLRP3-mediated cryopyrin-associated periodic syndromes (CAPS) release greater amounts of IL-1β than monocytes from unaffected subjects. Here we show that stress lowers the threshold of activation; blood monocytes from CAPS patients maintain the high levels of secreted IL-1β (fivefold) and IL-18 (10-fold) when stimulated with 1,000-fold less LPS than that required for full IL-1β secretion in control subjects. Unexpectedly, IL-1α secretion is increased 10-fold, indicating that inflammatory episodes in CAPS may not be entirely a result of IL-1β but may also involve IL-1α. In CAPS monocytes, LPS induces the externalization of copious amounts of ATP (10-fold), which drive IL-1β, IL-18, and IL-1α release via activation of the P2X purinoceptor 7. This enhanced ATP release appears to be the link between cell stress and increased cytokine secretion in CAPS. In the later phase after LPS stimulation, CAPS monocytes undergo oxidative stress, which impairs production of the anti-inflammatory IL-1 receptor antagonist (IL-1Ra). Remarkably, IL-1Ra secretion is fully restored by treatment with antioxidants. In two patients with the same NLRP3 mutation, but different disease severity, monocytes from the mildly affected patient exhibited more efficient redox response, lower ATP secretion, and more balanced cytokine production. Thus, the robustness of the individual antioxidant response increases the tolerance to stress and reduces the negative effect of the disease. Pharmacologic block of P2X purinoceptor 7 and improved stress tolerance may represent novel treatment strategies in stress-associated inflammatory diseases.
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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.