Inhibition of the NLRP3 Inflammasome Activation/Assembly through the Activation of the PI3K Pathway by Naloxone Protects Neural Stem Cells from Ischemic Condition
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Abstract
Naloxone is a well-known opioid antagonist and has been suggested to have neuroprotective effects in cerebral ischemia. We investigated whether naloxone exhibits anti-inflammatory and neuroprotective effects in neural stem cells (NSCs) injured by oxygen-glucose deprivation (OGD), whether it affects the NOD-like receptor protein 3 (NLRP3) inflammasome activation/assembly, and whether the role of the phosphatidylinositol 3-kinase (PI3K) pathway is important in the control of NLRP3 inflammasome activation/assembly by naloxone. Primary cultured NSCs were subjected to OGD and treated with different concentrations of naloxone. Cell viability, proliferation, and the intracellular signaling proteins associated with the PI3K pathway and NLRP3 inflammasome activation/assembly were evaluated in OGD-injured NSCs. OGD significantly reduced survival, proliferation, and migration and increased apoptosis of NSCs. However, treatment with naloxone significantly restored survival, proliferation, and migration and decreased apoptosis of NSCs. Moreover, OGD markedly increased NLRP3 inflammasome activation/assembly and cleaved caspase-1 and interleukin-1β levels in NSCs, but naloxone significantly attenuated these effects. These neuroprotective and anti-inflammatory effects of naloxone were eliminated when cells were treated with PI3K inhibitors. Our results suggest that NLRP3 inflammasome is a potential therapeutic target and that naloxone reduces ischemic injury in NSCs by inhibiting NLRP3 inflammasome activation/assembly mediated by the activation of the PI3K signaling pathway.
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Cites
Feigin, V. L., Forouzanfar, M. H., Krishnamurthi, R., Mensah, G. A., Connor, M., Bennett, D. A., Moran, A. E., Sacco, R. L., Anderson, L., Truelsen, T., et al. (2014) · The Lancet · doi:10.1016/s0140-6736(13)61953-4 · Cited by 3,899 · see citing works
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Mechanism of NLRP3 inflammasome activation
Sutterwala, F. S., Haasken, S., & Cassel, S. L. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12458 · Cited by 736 · see citing works
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Self-citationContinuous Infusion of Naloxone in the Treatment of Narcotic Overdose
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Flagged first, then by citations
- Authors
- Kim, J. Y., Hwang, M., Choi, N.-Y., & Koh, S.-H.
- Affiliations
- Hanyang University Guri Hospital (KR)
- Hanyang University (KR)
- Corresponding author
- Koh, Seong-Ho
- Venue
- Molecular Neurobiology
- Published
- 2023-06-10
- Volume
- 60
- Issue
- 9
- Pages
- 5330-5342
- ISSN
- 0893-7648 (ISSN-L)
- 1559-1182
- OpenAlex
- W4380153694
- Cited by
- 14
- References
- 5
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 3 · 2023: 1
- FWCI
- 1.25
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Molecular Neurobiology (publishedVersion)
- Research Square (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Ministry of Health & Welfare, Republic of Korea (HI20C0253, HU21C0007, and HU21C0113)
- Medical Research Center, Republic of Korea (2017R1A5A2015395)
- Korea government (2022R1F1A1072546, 2022R1A2C1092835)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Keywords
- naloxone, NLRP3 inflammasome, PI3K signaling, neural stem cells, cerebral ischemia, oxygen-glucose deprivation, neuroprotection, anti-inflammatory activity, caspase-1, IL-1β, apoptosis, stem cell proliferation and migration
- MeSH terms
- NLR Proteins, NLR Family, Pyrin Domain-Containing 3 Protein, Anti-Inflammatory Agents, Naloxone, Oxygen, Neuroprotective Agents, Phosphatidylinositol 3-Kinases, Phosphatidylinositol 3-Kinase, Inflammasomes, Neural Stem Cells
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