論文 - 詳細
| RRC ID | 63126 |
|---|---|
| 著者 | Okamura M, Shizu R, Abe T, Kodama S, Hosaka T, Sasaki T, Yoshinari K. |
| タイトル | PXR Functionally Interacts with NF-κB and AP-1 to Downregulate the Inflammation-Induced Expression of Chemokine CXCL2 in Mice. |
| ジャーナル | Cells |
| Abstract |
Pregnane X receptor (PXR) is a liver-enriched xenobiotic-responsive transcription factor. Although recent studies suggest that PXR shows anti-inflammatory effects by suppressing nuclear factor kappa B (NF-κB), the detailed mechanism remains unclear. In this study, we aimed to elucidate this mechanism. Mice were treated intraperitoneally with the PXR agonist pregnenolone 16α-carbonitrile (PCN) and/or carbon tetrachloride (CCl4). Liver injury was evaluated, and hepatic mRNA levels were determined via quantitative reverse transcription polymerase chain reaction. Reporter assays with wild-type and mutated mouse Cxcl2 promoter-containing reporter plasmids were conducted in 293T cells. Results showed that the hepatic expression of inflammation-related genes was upregulated in CCl4-treated mice, and PCN treatment repressed the induced expression of chemokine-encoding Ccl2 and Cxcl2 among the genes investigated. Consistently, PCN treatment suppressed the increased plasma transaminase activity and neutrophil infiltration in the liver. In reporter assays, tumor necrosis factor-α-induced Cxcl2 expression was suppressed by PXR. Although an NF-κB inhibitor or the mutation of an NF-κB-binding motif partly reduced PXR-dependent suppression, the mutation of both NF-κB and activator protein 1 (AP-1) sites abolished it. Consistently, AP-1-dependent gene transcription was suppressed by PXR with a construct containing AP-1 binding motifs. In conclusion, the present results suggest that PXR exerts anti-inflammatory effects by suppressing both NF-κB- and AP-1-dependent chemokine expression in mouse liver. |
| 巻・号 | 9(10) |
| 公開日 | 2020-10-15 |
| DOI | 10.3390/cells9102296 |
| PII | cells9102296 |
| PMID | 33076328 |
| PMC | PMC7602528 |
| MeSH | Animals Anti-Inflammatory Agents Carbon Tetrachloride / pharmacology Chemical and Drug Induced Liver Injury Chemokine CXCL2 / genetics* Disease Models, Animal Gene Expression Regulation HEK293 Cells Humans Inflammation / genetics* Male Mice Mice, Inbred C57BL NF-kappa B / metabolism* Pregnane X Receptor / metabolism* Pregnenolone Carbonitrile / pharmacology Protein Binding Transcription Factor AP-1 / metabolism* Tumor Necrosis Factor-alpha / metabolism |
| IF | 4.366 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 1 |
| 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 | 293T(RCB2202) |