ArticleCells2018
Extracellular Histones Activate Plasma Membrane Toll-Like Receptor 9 to Trigger Calcium Oscillations in Rat Pancreatic Acinar Tumor Cell AR4-2J.
Article in Cells, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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
19 citing papers in PubMed, 30 citations in OpenAlex.
- ILC2s regulate a fibroblast progenitor niche in the pancreas.Science (New York, N.Y.) · 2026Article
- Review
- Regulation of histones in thromboinflammation.Frontiers in immunology · 2026Review
- Pre-activation timing determines influenza severity and viral pathogenicity via STING Inhibition.Scientific reports · 2025Article
- TLR2 and TLR9 Blockade Using Specific Intrabodies Inhibits Inflammation-Mediated Pancreatic Cancer Cell Growth.Antibodies (Basel, Switzerland) · 2024Article
- Emerging therapeutic strategies targeting extracellular histones for critical and inflammatory diseases: an updated narrative review.Frontiers in immunology · 2024Review
- Identification and analysis of chemokine-related and NETosis-related genes in acute pancreatitis to develop a predictive model.Frontiers in genetics · 2024Article
- Photodynamic Activation of Cholecystokinin 1 Receptor Is Conserved in Mammalian and Avian Pancreatic Acini.Biomedicines · 2023Article
- Surface toll-like receptor 9 on immune cells and its immunomodulatory effect.Frontiers in immunology · 2023Review
- Systemic Bile Acids Affect the Severity of Acute Pancreatitis in Mice Depending on Their Hydrophobicity and the Disease Pathogenesis.International journal of molecular sciences · 2022Article
- Fighting Fire with Fire: Exosomes and Acute Pancreatitis-Associated Acute Lung Injury.Bioengineering (Basel, Switzerland) · 2022Review
- Mysteries and unsolved problems of mammalian fertilization and related topics.Biology of reproduction · 2022Review
- Epigenetics in Alzheimer's Disease.Frontiers in aging neuroscience · 2022Review
- [Advances in the role of extracellular histones in the inflammatory process of liver injury].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2021Review
- Systemic Immune-Inflammation Index (SII) Can Be an Early Indicator for Predicting the Severity of Acute Pancreatitis: A Retrospective Study.International journal of general medicine · 2021Article
- Extracellular histones stimulate collagen expressionWorld journal of gastroenterology · 2020Article
- Photodynamic Activation of Cholecystokinin 1 Receptor with Different Genetically Encoded Protein Photosensitizers and from Varied Subcellular Sites.Biomolecules · 2020Article
- NanoLuc Bioluminescence-Driven Photodynamic Activation of Cholecystokinin 1 Receptor with Genetically-Encoded Protein Photosensitizer MiniSOG.International journal of molecular sciences · 2020Article
- Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In acute pancreatitis, histones are released by infiltrating neutrophils, but how histones modulate pancreatic acinar cell function has not been investigated. We have examined histone modulation of rat pancreatic acini and pancreatic acinar tumor cell AR4-2J by calcium imaging. Histones were found to have no effect on calcium in pancreatic acini but blocked calcium oscillations induced by cholecystokinin or acetylcholine. Both mixed (Hx) and individual (H1, H2A, H2B, H3, H4) histones induced calcium oscillations in AR4-2J. RT-PCR and Western blot verified the expression of histone-targeted Toll-like receptor (TLR) 2, 4 and 9. Immunocytochemistry identified TLR2/TLR4 on apical plasma membrane and TLR9 in zymogen granule regions in pancreatic acini. TLR2 was found on neighboring and TLR9 on peripheral plasma membranes, but TLR4 was in the nucleus in AR4-2J clusters. Neither TLR2 agonist zymosan-A nor TLR4 agonist lipopolysaccharide had any effect on calcium, but TLR9 agonist ODN1826 induced calcium oscillations; TLR9 antagonist ODN2088 blocked H4-induced calcium oscillations in AR4-2J, which also disappeared after treatment of AR4-2J with glucocorticoid dexamethasone, with concurrent TLR9 migration from plasma membrane to cell interiors. TLR9 down regulation with siRNA suppressed H4-induced calcium oscillations. These data together suggest that extracellular histones activate plasma membrane TLR9 to trigger calcium oscillations in AR4-2J cells.
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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.