Interleukin-16 inhibits sodium channel function and GluA1 phosphorylation via CD4- and CD9-independent mechanisms to reduce hippocampal neuronal excitability and synaptic activity
Open accessAbstract
Interleukin 16 (IL-16) is a cytokine that is primarily associated with CD4+ T cell function, but also exists as a multi-domain PDZ protein expressed within cerebellar and hippocampal neurons. We have previously shown that lymphocyte-derived IL-16 is neuroprotective against excitotoxicity, but evidence of how it affects neuronal function is limited. Here, we have investigated whether IL-16 modulates neuronal excitability and synaptic activity in mouse primary hippocampal cultures. Application of recombinant IL-16 impairs both glutamate-induced increases in intracellular Ca 2+ and sEPSC frequency and amplitude in a CD4- and CD9-independent manner. We examined the mechanisms underlying these effects, with rIL-16 reducing GluA1 S831 phosphorylation and inhibiting Na+ channel function. Taken together, these data suggest that IL-16 reduces neuronal excitability and synaptic activity via multiple mechanisms and adds further evidence that alternative receptors may exist for IL-16.
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Interleukin 16 has been shown to reduce neuronal excitability and synaptic activity.
“The pro-inflammatory cytokine interleukin 16 has been shown to reduce neuronal excitability and synaptic activity (Hridi et al., 2019).”
From Epigenome-wide DNA methylation in unipolar depression: predictive biomarker of antidepressant treatment response? (2024) · cites this paper as Hridi et al., 2019
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- Authors
- Hridi, S. U., Franssen, A. J. P. M., Jiang, H.-R., & Bushell, T. J.
- Affiliations
- University of Strathclyde (GB)
- Corresponding author
- Bushell, Trevor J.
- Venue
- Molecular and Cellular Neuroscience
- Publisher
- Elsevier BV
- Published
- 2019-03
- Volume
- 95
- Pages
- 71-78
- ISSN
- 1044-7431 (ISSN-L)
- OpenAlex
- W2910781971
- Cited by
- 20
- References
- 54
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 2
- FWCI
- 1.08
- Type
- journal article
- Language
- en
- Open access
- Locations
- Molecular and Cellular Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Strathprints: The University of Strathclyde institutional repository (University of Strathclyde) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- interleukin-16, hippocampal neurons, neuronal excitability, synaptic activity, sodium channel inhibition, GluA1 phosphorylation, glutamate receptor subunits, intracellular calcium, excitatory postsynaptic currents, neuroprotection
- MeSH terms
- Animals, Calcium, Cells, Cultured, Hippocampus, Mice, Inbred C57BL, Neurons, Phosphorylation, Sodium Channels, CD4 Antigens, Receptors, AMPA, Neuroprotective Agents, Glutamic Acid, Interleukin-16, Excitatory Postsynaptic Potentials, Mice, Tetraspanin 29
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