Interleukin-16 inhibits sodium channel function and GluA1 phosphorylation via CD4- and CD9-independent mechanisms to reduce hippocampal neuronal excitability and synaptic activity

Shehla U. Hridi, Aimée J.P.M. Franssen, Hui-Rong Jiang, Trevor J. Bushell

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Abstract

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 Ca2+ 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.
Original languageEnglish
Pages (from-to)71-78
Number of pages8
JournalMolecular and Cellular Neuroscience
Volume95
Early online date7 Feb 2019
DOIs
Publication statusPublished - 31 Mar 2019

Keywords

  • IL-16
  • CD4
  • neuron
  • calcium signalling
  • na+ channels
  • sEPSCs

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