Cargando…
TAAR1 Expression in Human Macrophages and Brain Tissue: A Potential Novel Facet of MS Neuroinflammation
TAAR1 is a neuroregulator with emerging evidence suggesting a role in immunomodulation. Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. Here, we investigate TAAR1 expression in human primary monocytes, peripherally-derived macrophages, and MS brain...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584001/ https://www.ncbi.nlm.nih.gov/pubmed/34769007 http://dx.doi.org/10.3390/ijms222111576 |
_version_ | 1784597340400648192 |
---|---|
author | Barnes, David A. Galloway, Dylan A. Hoener, Marius C. Berry, Mark D. Moore, Craig S. |
author_facet | Barnes, David A. Galloway, Dylan A. Hoener, Marius C. Berry, Mark D. Moore, Craig S. |
author_sort | Barnes, David A. |
collection | PubMed |
description | TAAR1 is a neuroregulator with emerging evidence suggesting a role in immunomodulation. Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. Here, we investigate TAAR1 expression in human primary monocytes, peripherally-derived macrophages, and MS brain tissue. RT-qPCR was used to assess TAAR1 levels in MS monocytes. Using a previously validated anti-human TAAR1 antibody and fluorescence microscopy, TAAR1 protein was visualized in lipopolysaccharide-stimulated or basal human macrophages, as well as macrophage/microglia populations surrounding, bordering, and within a mixed active/inactive MS lesion. In vivo, TAAR1 mRNA expression was significantly lower in MS monocytes compared to age- and sex-matched healthy controls. In vitro, TAAR1 protein showed a predominant nuclear localization in quiescent/control macrophages with a shift to a diffuse intracellular distribution following lipopolysaccharide-induced activation. In brain tissue, TAAR1 protein was predominantly expressed in macrophages/microglia within the border region of mixed active/inactive MS lesions. Considering that TAAR1-mediated anti-inflammatory effects have been previously reported, decreased mRNA in MS patients suggests possible pathophysiologic relevance. A shift in TAAR1 localization following pro-inflammatory activation suggests its function is altered in pro-inflammatory states, while TAAR1-expressing macrophages/microglia bordering an MS lesion supports TAAR1 as a novel pharmacological target in cells directly implicated in MS neuroinflammation. |
format | Online Article Text |
id | pubmed-8584001 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85840012021-11-12 TAAR1 Expression in Human Macrophages and Brain Tissue: A Potential Novel Facet of MS Neuroinflammation Barnes, David A. Galloway, Dylan A. Hoener, Marius C. Berry, Mark D. Moore, Craig S. Int J Mol Sci Communication TAAR1 is a neuroregulator with emerging evidence suggesting a role in immunomodulation. Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. Here, we investigate TAAR1 expression in human primary monocytes, peripherally-derived macrophages, and MS brain tissue. RT-qPCR was used to assess TAAR1 levels in MS monocytes. Using a previously validated anti-human TAAR1 antibody and fluorescence microscopy, TAAR1 protein was visualized in lipopolysaccharide-stimulated or basal human macrophages, as well as macrophage/microglia populations surrounding, bordering, and within a mixed active/inactive MS lesion. In vivo, TAAR1 mRNA expression was significantly lower in MS monocytes compared to age- and sex-matched healthy controls. In vitro, TAAR1 protein showed a predominant nuclear localization in quiescent/control macrophages with a shift to a diffuse intracellular distribution following lipopolysaccharide-induced activation. In brain tissue, TAAR1 protein was predominantly expressed in macrophages/microglia within the border region of mixed active/inactive MS lesions. Considering that TAAR1-mediated anti-inflammatory effects have been previously reported, decreased mRNA in MS patients suggests possible pathophysiologic relevance. A shift in TAAR1 localization following pro-inflammatory activation suggests its function is altered in pro-inflammatory states, while TAAR1-expressing macrophages/microglia bordering an MS lesion supports TAAR1 as a novel pharmacological target in cells directly implicated in MS neuroinflammation. MDPI 2021-10-27 /pmc/articles/PMC8584001/ /pubmed/34769007 http://dx.doi.org/10.3390/ijms222111576 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Barnes, David A. Galloway, Dylan A. Hoener, Marius C. Berry, Mark D. Moore, Craig S. TAAR1 Expression in Human Macrophages and Brain Tissue: A Potential Novel Facet of MS Neuroinflammation |
title | TAAR1 Expression in Human Macrophages and Brain Tissue: A Potential Novel Facet of MS Neuroinflammation |
title_full | TAAR1 Expression in Human Macrophages and Brain Tissue: A Potential Novel Facet of MS Neuroinflammation |
title_fullStr | TAAR1 Expression in Human Macrophages and Brain Tissue: A Potential Novel Facet of MS Neuroinflammation |
title_full_unstemmed | TAAR1 Expression in Human Macrophages and Brain Tissue: A Potential Novel Facet of MS Neuroinflammation |
title_short | TAAR1 Expression in Human Macrophages and Brain Tissue: A Potential Novel Facet of MS Neuroinflammation |
title_sort | taar1 expression in human macrophages and brain tissue: a potential novel facet of ms neuroinflammation |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584001/ https://www.ncbi.nlm.nih.gov/pubmed/34769007 http://dx.doi.org/10.3390/ijms222111576 |
work_keys_str_mv | AT barnesdavida taar1expressioninhumanmacrophagesandbraintissueapotentialnovelfacetofmsneuroinflammation AT gallowaydylana taar1expressioninhumanmacrophagesandbraintissueapotentialnovelfacetofmsneuroinflammation AT hoenermariusc taar1expressioninhumanmacrophagesandbraintissueapotentialnovelfacetofmsneuroinflammation AT berrymarkd taar1expressioninhumanmacrophagesandbraintissueapotentialnovelfacetofmsneuroinflammation AT moorecraigs taar1expressioninhumanmacrophagesandbraintissueapotentialnovelfacetofmsneuroinflammation |