Cited by 223Neuroinflammation and Neurodegeneration MechanismsDrug Transport and Resistance MechanismsPain Mechanisms and Treatments

TUDCA: An Agonist of the Bile Acid Receptor GPBAR1/TGR5 With Anti‐Inflammatory Effects in Microglial Cells

Yanguas‐Casás, Natalia, Barreda‐Manso, M. Asunción, Nieto‐Sampedro, Manuel, Romero‐Ramírez, Lorenzo·2017·Journal of Cellular Physiology

Abstract

Bile acids are steroid acids found in the bile of mammals. The bile acid conjugate tauroursodeoxycholic acid (TUDCA) is neuroprotective in different animal models of stroke and neurological diseases. We have previously shown that TUDCA has anti‐inflammatory effects on glial cell cultures and in a mouse model of acute neuroinflammation. We show now that microglial cells (central nervous system resident macrophages) express the G protein‐coupled bile acid receptor 1/Takeda G protein‐coupled receptor 5 (GPBAR1/TGR5) in vivo and in vitro. TUDCA binding to GPBAR1/TGR5 caused an increase in intracellular cAMP levels in microglia that induced anti‐inflammatory markers, while reducing pro‐inflammatory ones. This anti‐inflammatory effect of TUDCA was inhibited by small interference RNA for GPBAR1/TGR5 receptor, as well as by treatment with a protein kinase A (PKA) inhibitor. In the mouse model of acute neuroinflammation, treating the animals with TUDCA was clearly anti‐inflammatory. TUDCA biased the microglial phenotype in vivo and in vitro toward the anti‐inflammatory. The bile acid receptor GPBAR1/TGR5 could be a new therapeutic target for pathologies coursing with neuroinflammation and microglia activation, such as traumatic brain injuries, stroke, or neurodegenerative diseases. TUDCA and other GPBAR1/TGR5 agonists need to be further investigated, to determine their potential in attenuating the neuropathologies associated with microglia activation. J. Cell. Physiol. 232: 2231–2245, 2017. © 2016 Wiley Periodicals, Inc.

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Crossref · 10.1002/jcp.25742

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Authors
Yanguas‐Casás, N., Barreda‐Manso, M. A., Nieto‐Sampedro, M., & Romero‐Ramírez, L.
Affiliations
  • Consejo Superior de Investigaciones Científicas (ES)
  • Departamento de Neurobiología Funcional y de Sistemas Instituto Cajal (CSIC) Madrid Spain
  • Servicio de Salud de Castilla La Mancha (ES)
Corresponding author
Romero‐Ramírez, Lorenzo
Venue
Journal of Cellular Physiology
Publisher
Wiley
Published
2017-03-03
Volume
232
Issue
8
Pages
2231-2245
ISSN
  • 0021-9541 (ISSN-L)
  • 1097-4652
OpenAlex
W2565880658
Cited by
223
References
69
Citations by year
2026: 19 · 2025: 33 · 2024: 30 · 2023: 25 · 2022: 34 · 2021: 29 · 2020: 27 · 2019: 12 · 2018: 10 · 2017: 4
FWCI
4.75
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Cellular Physiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Ministerio de Ciencia e Innovación (SAF2009‐11257)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Keywords
tauroursodeoxycholic acid, bile acid receptors, microglia, neuroinflammation, anti-inflammatory activity, cAMP signaling, protein kinase A, receptor agonists, microglial activation, traumatic brain injury, stroke, neurodegenerative diseases
MeSH terms
Cyclic AMP, Animals, Animals, Newborn, Anti-Inflammatory Agents, Cells, Cultured, Disease Models, Animal, Encephalitis, Hippocampus, Mice, Inbred C57BL, Taurochenodeoxycholic Acid, Time Factors, Transfection, Signal Transduction, Prosencephalon, Rats, Wistar, Microglia, Cyclic AMP-Dependent Protein Kinases, Neuroprotective Agents, Inflammation Mediators, RNA Interference, Receptors, G-Protein-Coupled, Protein Kinase Inhibitors

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