ArticleMediators of inflammation2016
Inhibition of Extracellular Calcium Influx Results in Enhanced IL-12 Production in LPS-Treated Murine Macrophages by Downregulation of the CaMKKβ-AMPK-SIRT1 Signaling Pathway.
Article in Mediators of inflammation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
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- Novel 3-D macrophage spheroid model reveals reciprocal regulation of immunomechanical stress and mechano-immunological response.bioRxiv : the preprint server for biology · 2024Article
- Investigation of local stimulation effects of embedding PGLA at Zusanli (ST36) acupoint in rats based on TRPV2 and TRPV4 ion channels.Frontiers in neuroscience · 2024Article
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- Stimulus-Specific Expression, Selective Generation and Novel Function of Grass Carp (Frontiers in immunology · 2021Article
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- Momordica charantia polysaccharides modulate the differentiation of neural stem cells via SIRT1/Β-catenin axis in cerebral ischemia/reperfusion.Stem cell research & therapy · 2020Article
- ASGR1 and Its Enigmatic Relative, CLEC10A.International journal of molecular sciences · 2020Review
- Identification of circRNA and mRNA expression profiles and functional networks of vascular tissue in lipopolysaccharide-induced sepsis.Journal of cellular and molecular medicine · 2020Article
- Stories From the Dendritic Cell Guardhouse.Frontiers in immunology · 2019Review
- Inhibition of NF-κB Signaling Pathway by Resveratrol Improves Spinal Cord Injury.Frontiers in neuroscience · 2018Review
- STIM Proteins and Orai CaFrontiers in pharmacology · 2018Article
- Silver Nanoparticles Against Salmonella enterica Serotype Typhimurium: Role of Inner Membrane Dysfunction.Current microbiology · 2017Article
- NADPH oxidase 2 inhibitor diphenyleneiodonium enhances ROS-independent bacterial phagocytosis in murine macrophages via activation of the calcium-mediated p38 MAPK signaling pathway.American journal of translational research · 2017Article
- The citrus flavonoid naringenin confers protection in a murine endotoxaemia model through AMPK-ATF3-dependent negative regulation of the TLR4 signalling pathway.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activated macrophages are the primary sources of IL-12, a key cytokine bridging innate and adaptive immunity. However, macrophages produce low amounts of IL-12 upon stimulation and the underlying regulatory mechanism remains unclear. In this study, we found a new calcium-dependent mechanism that controlled IL-12 production in LPS-treated murine macrophages. First, LPS was demonstrated to induce extracellular calcium entry in murine peritoneal macrophages and inhibition of calcium influx resulted in marked enhancement in IL-12 production. Then, withdrawal of extracellular calcium was found to suppress CaMKKβ and AMPK activation triggered by LPS while chemical inhibition or genetic knockdown of these two kinases augmented LPS induced IL-12 production. AMPK activation increased the NAD(+)/NADH ratio and activated Sirtuin 1 (SIRT1), a NAD(+)-dependent deacetylating enzyme and negative regulator of inflammation. Chemical inhibitor or siRNA of SIRT1 enhanced IL-12 release while its agonist suppressed IL-12 production. Finally, it was found that SIRT1 selectively affected the transcriptional activity of NF-κB which thereby inhibited IL-12 production. Overall, our study demonstrates a new role of transmembrane calcium mobilization in immunity modulation such that inhibition of calcium influx leads to impaired activation of CaMKKβ-AMPK-SIRT1 signaling pathway which lifts restriction on NF-κB activation and results in enhanced IL-12 production.
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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.