論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Jurkat(RCB3052) |