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

Research output: Contribution to journalArticle

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.
LanguageEnglish
Pages71-78
Number of pages8
JournalMolecular and Cellular Neuroscience
Volume95
Early online date7 Feb 2019
DOIs
Publication statusPublished - 31 Mar 2019

Fingerprint

Interleukin-16
Sodium Channels
Phosphorylation
PDZ Domains
Glutamic Acid
Lymphocytes
Cytokines
T-Lymphocytes
Neurons

Keywords

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

Cite this

@article{c6eb56ef83e04ac39c90c1e566b4aeb5,
title = "Interleukin-16 inhibits sodium channel function and GluA1 phosphorylation via CD4- and CD9-independent mechanisms to reduce hippocampal neuronal excitability and synaptic activity",
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.",
keywords = "IL-16, CD4, neuron, calcium signalling, na+ channels, sEPSCs",
author = "Hridi, {Shehla U.} and Franssen, {Aim{\'e}e J.P.M.} and Hui-Rong Jiang and Bushell, {Trevor J.}",
year = "2019",
month = "3",
day = "31",
doi = "10.1016/j.mcn.2019.01.002",
language = "English",
volume = "95",
pages = "71--78",
journal = "Molecular and Cellular Neuroscience",
issn = "1044-7431",

}

TY - JOUR

T1 - Interleukin-16 inhibits sodium channel function and GluA1 phosphorylation via CD4- and CD9-independent mechanisms to reduce hippocampal neuronal excitability and synaptic activity

AU - Hridi, Shehla U.

AU - Franssen, Aimée J.P.M.

AU - Jiang, Hui-Rong

AU - Bushell, Trevor J.

PY - 2019/3/31

Y1 - 2019/3/31

N2 - 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.

AB - 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.

KW - IL-16

KW - CD4

KW - neuron

KW - calcium signalling

KW - na+ channels

KW - sEPSCs

UR - https://www.sciencedirect.com/journal/molecular-and-cellular-neuroscience

U2 - 10.1016/j.mcn.2019.01.002

DO - 10.1016/j.mcn.2019.01.002

M3 - Article

VL - 95

SP - 71

EP - 78

JO - Molecular and Cellular Neuroscience

T2 - Molecular and Cellular Neuroscience

JF - Molecular and Cellular Neuroscience

SN - 1044-7431

ER -