Expression and function of the bile acid receptor TGR5 in Kupffer cells
Abstract
Kupffer cells are resident macrophages in the liver and play a central role in the hepatic response to injury. Bile acids can impair macrophage function leading to decreased cytokine release. TGR5 is a novel, membrane-bound bile acid receptor, and it has been suggested that the immunosuppressive effect of bile acids can be mediated by TGR5. However, the function of TGR5 in Kupffer cells has not been studied and a direct link between TGR5 and cytokine production in macrophages has not been established. The present study demonstrates that TGR5 is localized in the plasma membrane of isolated Kupffer cells and is responsive to bile acids. Furthermore, bile acids inhibited LPS-induced cytokine expression in Kupffer cells via TGR5-cAMP dependent pathways. TGR5-immunoreactivity in Kupffer cells was increased in rat livers following bile-duct ligation, suggesting that TGR5 may play a protective role in obstructive cholestasis preventing excessive cytokine production thereby reducing liver injury.
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Activation of GPBAR1 on macrophages and Kupffer cells by synthetic agonists inhibits LPS-induced pro-inflammatory cytokines by interfering with NF-κB-dependent transcription.
“activation of GPBAR1 on macrophages and Kupffer cells by synthetic agonists inhibits the expression of LPS-induced pro-inflammatory cytokines by interfering with NF-κB-dependent transcription.”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Keitel et al., 2008
This inhibition has been linked to direct inhibition of NF-κB activation but is also consistent with transcriptional competition between NF-κB and CREB.
“This has been linked to direct inhibition of NF-κB activation, but is also consistent with a model of transcriptional competition between NF-κB and the cAMP-activated transcription factor cAMP response element binding protein (CREB) (C. Guo et al., 2015; Kawamata et al., 2003; Keitel et al., 2008; Pols et al., 2011; Y.-D. Wang et al., 2011; Wen et al., 2010).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Keitel et al., 2008
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- Authors
- Keitel, V., Donner, M., Winandy, S., Kubitz, R., & Häussinger, D.
- Affiliations
- Heinrich Heine University Düsseldorf (DE)
- Corresponding author
- Häussinger, Dieter
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2008-07
- Volume
- 372
- Issue
- 1
- Pages
- 78-84
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2017362076
- Cited by
- 418
- References
- 38
- Citations by year
- 2026: 20 · 2025: 23 · 2024: 26 · 2023: 18 · 2022: 21 · 2021: 33 · 2020: 30 · 2019: 22 · 2018: 29 · 2017: 29 · 2016: 20 · 2015: 24 · 2014: 25 · 2013: 31 · 2012: 20
- FWCI
- 8.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- TGR5, bile acid receptors, Kupffer cells, macrophages, bile acids, cytokine production, lipopolysaccharide-induced inflammation, cAMP signaling, plasma membrane localization, bile duct ligation, obstructive cholestasis, liver injury, immunosuppression
- MeSH terms
- Animals, Bile Acids and Salts, Cell Line, Cell Membrane, Humans, Kupffer Cells, Liver, Transfection, Cytokines, Rats, Wistar, Receptors, G-Protein-Coupled, Rats
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