Expression and function of the bile acid receptor TGR5 in Kupffer cells
Section snippets
Materials and methods
Materials. Cell culture media were from Gibco (Invitrogen, Karlsruhe, Germany). Penicillin/streptomycin were from Biochrom (Berlin, Germany). Foetal calf serum was from PAA (Coelbe, Germany). Taurocholate, taurolithocholate, oleanoloic acid were from Sigma–Aldrich (Taufkirchen, Germany). The TGR5 agonist BR27 was a gift from the Bayer AG (Leverkusen, Germany).
Antibodies. Polyclonal antibodies were raised in guinea pigs (M38) and rabbits (K36) against amino acids 306–329 from the C-terminus of
Localization of TGR5 in rat liver
Immunolocalization of TGR5 was studied in rat livers using an antibody directed against the C-terminus of rat TGR5 [11]. TGR5-immunoreactivity was detected in sinusoidal endothelial cells and in Kupffer cells (KC); the latter was shown by the co-localization of the TGR5 specific staining with the CD163 (ED2) fluorescence pattern, a common marker protein of KC (Fig. 1A–C). Furthermore, TGR5 was localized in cytokeratin-19 (CK19)-expressing bile-ducts [22], as demonstrated by the co-localization
Discussion
As shown previously, the bile acid receptor TGR5 is expressed in sinusoidal endothelial cells (SEC), where bile acids induced expression of eNOS mRNA and increased NO production [11]. Expression of TGR5 was also found in Kupffer cells (KC) [11], but the functional significance of TGR5 in KC remained unclear to date. The present study addressed this issue and demonstrates that TGR5 is localized in the plasma membrane of isolated KC and is activated in response to bile acids leading to increased
Acknowledgments
This study was supported by the Deutsche Forschungsgemeinschaft through Sonderforschungsbereich 575 “Experimental Hepatology” and through the Forschungskommission Düsseldorf. Expert technical assistance by Claudia Rupprecht is acknowledged.
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