Bibliographic Details
| Title: |
β-Defensin 1 Is Prominent in the Liver and Induced During Cholestasis by Bilirubin and Bile Acids via Farnesoid X Receptor and Constitutive Androstane Receptor |
| Authors: |
Thomas Klag, Maria Thomas, Dirk Ehmann, Lioba Courth, Daniela Mailänder-Sanchez, Thomas S. Weiss, Rania Dayoub, Kerstin Abshagen, Brigitte Vollmar, Wolfgang E. Thasler, Eduard F. Stange, Christoph P. Berg, Nisar P. Malek, Ulrich M. Zanger, Jan Wehkamp |
| Source: |
Frontiers in Immunology, Vol 9 (2018) |
| Publisher Information: |
Frontiers Media S.A., 2018. |
| Publication Year: |
2018 |
| Collection: |
LCC:Immunologic diseases. Allergy |
| Subject Terms: |
cholestasis, antimicrobial peptides, human β-defensin-1, hepatocytes, bilirubin, Immunologic diseases. Allergy, RC581-607 |
| More Details: |
Background & aimsKnowledge about innate antimicrobial defense of the liver is limited. We investigated hepatic expression and regulation of antimicrobial peptides with focus on the human beta defensin-1 (hBD-1).MethodsRadial diffusion assay was used to analyze antimicrobial activity of liver tissue. Different defensins including hBD-1 and its activator thioredoxin-1 (TXN) were analyzed in healthy and cholestatic liver samples by qPCR and immunostaining. Regulation of hBD-1 expression was studied in vitro and in vivo using bile duct-ligated mice. Regulation of hBD-1 via bilirubin and bile acids (BAs) was studied using siRNA.ResultsWe found strong antimicrobial activity of liver tissue against Escherichia coli. As a potential mediator of this antimicrobial activity we detected high expression of hBD-1 and TXN in hepatocytes, whereas other defensins were minimally expressed. Using a specific antibody for the reduced, antimicrobially active form of hBD-1 we found hBD-1 in co-localization with TXN within hepatocytes. hBD-1 was upregulated in cholestasis in a graded fashion. In cholestatic mice hepatic AMP expression (Defb-1 and Hamp) was enhanced. Bilirubin and BAs were able to induce hBD-1 in hepatic cell cultures in vitro. Treatment with siRNA and/or agonists demonstrated that the farnesoid X receptor (FXR) mediates basal expression of hBD-1, whereas both constitutive androstane receptor (CAR) and FXR seem to be responsible for the induction of hBD-1 by bilirubin.ConclusionhBD-1 is prominently expressed in hepatocytes. It is induced during cholestasis through bilirubin and BAs, mediated by CAR and especially FXR. Reduction by TXN activates hBD-1 to a potential key player in innate antimicrobial defense of the liver. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1664-3224 |
| Relation: |
https://www.frontiersin.org/article/10.3389/fimmu.2018.01735/full; https://doaj.org/toc/1664-3224 |
| DOI: |
10.3389/fimmu.2018.01735 |
| Access URL: |
https://doaj.org/article/758afb4f1b044c01a3cc3e8ddec592b7 |
| Accession Number: |
edsdoj.758afb4f1b044c01a3cc3e8ddec592b7 |
| Database: |
Directory of Open Access Journals |
