Divergent Neuroinflammatory Regulation of Microglial TREM Expression and Involvement of NF-κB

The triggering receptor expressed on myeloid cells (TREM) family of proteins are cell surface receptors with important roles in regulation of myeloid cell inflammatory activity. In the central nervous system, TREM2 is implicated in further roles in microglial homeostasis, neuroinflammation and neuro...

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Publicado en:Front Cell Neurosci
Main Authors: Owens, Rosie, Grabert, Kathleen, Davies, Claire L., Alfieri, Alessio, Antel, Jack P., Healy, Luke M., McColl, Barry W.
Formato: Artigo
Idioma:Inglês
Publicado: Frontiers Media S.A. 2017
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Neuroscience
Acceso en liña:https://ncbi.nlm.nih.gov/pmc/articles/PMC5332401/
https://ncbi.nlm.nih.gov/pubmed/28303091
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.3389/fncel.2017.00056
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spelling pubmed-53324012017-03-16 Divergent Neuroinflammatory Regulation of Microglial TREM Expression and Involvement of NF-κB Owens, Rosie Grabert, Kathleen Davies, Claire L. Alfieri, Alessio Antel, Jack P. Healy, Luke M. McColl, Barry W. Front Cell Neurosci Neuroscience The triggering receptor expressed on myeloid cells (TREM) family of proteins are cell surface receptors with important roles in regulation of myeloid cell inflammatory activity. In the central nervous system, TREM2 is implicated in further roles in microglial homeostasis, neuroinflammation and neurodegeneration. Different TREM receptors appear to have contrasting roles in controlling myeloid immune activity therefore the relative and co-ordinated regulation of their expression is important to understand but is currently poorly understood. We sought to determine how microglial TREM expression is affected under neuroinflammatory conditions in vitro and in vivo. Our data show that microglial Trem1 and Trem2 gene expression are regulated in an opposing manner by lipopolysaccharide (LPS) in vitro in both adult murine and human microglia. LPS caused a significant induction of Trem1 and a contrasting suppression of Trem2 expression. We also observed similar divergent Trem1 and Trem2 responses in vivo in response to acute brain inflammation and acute cerebral ischaemia. Our data show that inhibition of NF-κB activation prevents the LPS-induced alterations in both Trem1 and Trem2 expression in vitro indicating NF-κB as a common signaling intermediate controlling these divergent responses. Distinct patterns of microglial Trem1 induction and Trem2 suppression to different Toll-like receptor (TLR) ligands were also evident, notably with Trem1 induction restricted to those ligands activating TLRs signaling via TRIF. Our data show co-ordinated but divergent regulation of microglial TREM receptor expression with a central role for NF-κB. Neuroinflammatory conditions that alter the balance in TREM expression could therefore be an important influence on microglial inflammatory and homeostatic activity with implications for neuroinflammatory and neurodegenerative disease. Frontiers Media S.A. 2017-03-02 /pmc/articles/PMC5332401/ /pubmed/28303091 http://dx.doi.org/10.3389/fncel.2017.00056 Text en Copyright © 2017 Owens, Grabert, Davies, Alfieri, Antel, Healy and McColl. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
institution US NLM
collection PubMed Central
language Inglês
format Artigo
topic Neuroscience
spellingShingle Neuroscience
Owens, Rosie
Grabert, Kathleen
Davies, Claire L.
Alfieri, Alessio
Antel, Jack P.
Healy, Luke M.
McColl, Barry W.
Divergent Neuroinflammatory Regulation of Microglial TREM Expression and Involvement of NF-κB
description The triggering receptor expressed on myeloid cells (TREM) family of proteins are cell surface receptors with important roles in regulation of myeloid cell inflammatory activity. In the central nervous system, TREM2 is implicated in further roles in microglial homeostasis, neuroinflammation and neurodegeneration. Different TREM receptors appear to have contrasting roles in controlling myeloid immune activity therefore the relative and co-ordinated regulation of their expression is important to understand but is currently poorly understood. We sought to determine how microglial TREM expression is affected under neuroinflammatory conditions in vitro and in vivo. Our data show that microglial Trem1 and Trem2 gene expression are regulated in an opposing manner by lipopolysaccharide (LPS) in vitro in both adult murine and human microglia. LPS caused a significant induction of Trem1 and a contrasting suppression of Trem2 expression. We also observed similar divergent Trem1 and Trem2 responses in vivo in response to acute brain inflammation and acute cerebral ischaemia. Our data show that inhibition of NF-κB activation prevents the LPS-induced alterations in both Trem1 and Trem2 expression in vitro indicating NF-κB as a common signaling intermediate controlling these divergent responses. Distinct patterns of microglial Trem1 induction and Trem2 suppression to different Toll-like receptor (TLR) ligands were also evident, notably with Trem1 induction restricted to those ligands activating TLRs signaling via TRIF. Our data show co-ordinated but divergent regulation of microglial TREM receptor expression with a central role for NF-κB. Neuroinflammatory conditions that alter the balance in TREM expression could therefore be an important influence on microglial inflammatory and homeostatic activity with implications for neuroinflammatory and neurodegenerative disease.
author Owens, Rosie
Grabert, Kathleen
Davies, Claire L.
Alfieri, Alessio
Antel, Jack P.
Healy, Luke M.
McColl, Barry W.
author_facet Owens, Rosie
Grabert, Kathleen
Davies, Claire L.
Alfieri, Alessio
Antel, Jack P.
Healy, Luke M.
McColl, Barry W.
author_sort Owens, Rosie
title Divergent Neuroinflammatory Regulation of Microglial TREM Expression and Involvement of NF-κB
title_short Divergent Neuroinflammatory Regulation of Microglial TREM Expression and Involvement of NF-κB
title_full Divergent Neuroinflammatory Regulation of Microglial TREM Expression and Involvement of NF-κB
title_fullStr Divergent Neuroinflammatory Regulation of Microglial TREM Expression and Involvement of NF-κB
title_full_unstemmed Divergent Neuroinflammatory Regulation of Microglial TREM Expression and Involvement of NF-κB
title_sort divergent neuroinflammatory regulation of microglial trem expression and involvement of nf-κb
publisher Frontiers Media S.A.
container_title Front Cell Neurosci
publishDate 2017
url https://ncbi.nlm.nih.gov/pmc/articles/PMC5332401/
https://ncbi.nlm.nih.gov/pubmed/28303091
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.3389/fncel.2017.00056
_version_ 1818932779758387200

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