| RRC ID |
72189
|
| 著者 |
Shimoyama S, Kawata K, Ohta K, Chida T, Suzuki T, Tsuneyama K, Shimoda S, Kurono N, Leung PSC, Gershwin ME, Suda T, Kobayashi Y.
|
| タイトル |
Ursodeoxycholic acid impairs liver-infiltrating T-cell chemotaxis through IFN-γ and CX3CL1 production in primary biliary cholangitis.
|
| ジャーナル |
Eur J Immunol
|
| Abstract |
Ursodeoxycholic acid (UDCA) is the primary treatment for primary biliary cholangitis (PBC), but its mechanism of action remains unclear. Studies suggest that UDCA enhances NF erythroid 2-related factor 2 (NFE2L2) expression and that the interaction between IFN-γ and C-X3-C motif chemokine ligand 1 (CX3CL1) facilitates biliary inflammation in PBC. Therefore, we examined the effects of UDCA on the expression of IFN-γ and CX3CL1 in in vitro and in vivo PBC models such as human liver tissue, a murine model, cell lines, and isolated human intrahepatic biliary epithelial cells (IHBECs). We observed a significant decrease in IFN-γ mRNA levels and positive correlations between IFN-γ and CX3CL1 mRNA levels post-UDCA treatment in PBC livers. NFE2L2-mediated transcriptional activation was significantly enhanced in UDCA-treated Jurkat cells. In 2-octynoic acid-immunized mice, IFN-γ production by liver-infiltrating T cells was dependent on NFE2L2 activation. IFN-γ significantly and dose-dependentlyinduced CX3CL1 expression, which was significantly decreased in HuCC-T1 cells and IHBECs upon UDCA treatment. These results suggest that UDCA-induced suppression of IFN-γ and CX3CL1 production attenuates the chemotactic and adhesive abilities of liver-infiltrating T cells in PBC.
|
| 巻・号 |
51(6)
|
| ページ |
1519-1530
|
| 公開日 |
2021-6-1
|
| DOI |
10.1002/eji.202048589
|
| PMID |
33710617
|
| MeSH |
Adult
Aged
Aged, 80 and over
Chemokine CX3CL1 / metabolism*
Chemotaxis
Cholagogues and Choleretics / therapeutic use*
Epithelial Cells / physiology*
Female
Humans
Immunosuppression Therapy
Interferon-gamma / genetics
Interferon-gamma / metabolism*
Jurkat Cells
Liver / immunology*
Liver / pathology
Liver Cirrhosis, Biliary / drug therapy*
Liver Cirrhosis, Biliary / immunology
Male
Middle Aged
T-Lymphocytes / immunology*
Ursodeoxycholic Acid / therapeutic use*
|
| IF |
4.404
|
| リソース情報 |
| ヒト・動物細胞 |
Jurkat(RCB3052) |
