論文 - 詳細
| RRC ID | 44427 |
|---|---|
| 著者 | Yoshigai E, Hara T, Inaba H, Hashimoto I, Tanaka Y, Kaibori M, Kimura T, Okumura T, Kwon AH, Nishizawa M. |
| タイトル | Interleukin-1β induces tumor necrosis factor-α secretion from rat hepatocytes. |
| ジャーナル | Hepatol Res |
| Abstract |
AIM:Tumor necrosis factor-α (TNF-α) is a pleiotropic cytokine involved in various inflammatory diseases. The only production of TNF-α in the liver is thought to be from hepatic macrophages known as Kupffer cells, predominantly in response to bacterial lipopolysaccharide (LPS). METHODS:Primary cultured rat hepatocytes were used to analyze TNF-α expression in response to the pro-inflammatory cytokine, interleukin-1β (IL-1β). Livers of rats subjected to LPS-induced endotoxemia were analyzed. RESULTS:Immunocytochemistry and enzyme-linked immunosorbent assays demonstrated that IL-1β-treated rat hepatocytes secreted TNF-α, and RNA analyses indicated that TNF-α mRNA was induced specifically by IL-1β. Northern blot analysis showed that not only mRNA, but also a natural antisense transcript (asRNA), was transcribed from the rat Tnf gene in IL-1β-treated hepatocytes. TNF-α was detected in the hepatocytes of LPS-treated rats. Both TNF-α mRNA and asRNA were expressed in the hepatocytes of LPS-treated rats, human hepatocellular carcinoma and human monocyte/macrophage cells. To disrupt the interaction between TNF-α asRNA and TNF-α mRNA, sense oligonucleotides corresponding to TNF-α mRNA were introduced into rat hepatocytes resulting in significantly increased levels of TNF-α mRNA. One of these sense oligonucleotides increased a half-life of TNF-α mRNA, suggesting that the TNF-α asRNA may reduce the stability of TNF-α mRNA. CONCLUSION:IL-1β-stimulated rat hepatocytes are a newly identified source of TNF-α in the liver. TNF-α mRNA and asRNA are expressed in rats and humans, and the TNF-α asRNA reduces the stability of the TNF-α mRNA. Hepatocytes and TNF-α asRNA may be therapeutic targets to regulate levels of TNF-α mRNA. |
| 巻・号 | 44(5) |
| ページ | 571-83 |
| 公開日 | 2014-5-1 |
| DOI | 10.1111/hepr.12157 |
| PMID | 23647831 |
| IF | 3.165 |
| 引用数 | 31 |
| WOS 分野 | GASTROENTEROLOGY & HEPATOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | THP-1(RCB1189) |