| First Author | McMullen MR | Year | 2005 |
| Journal | Gastroenterology | Volume | 128 |
| Issue | 7 | Pages | 2066-76 |
| PubMed ID | 15940638 | Mgi Jnum | J:105638 |
| Mgi Id | MGI:3616144 | Doi | 10.1053/j.gastro.2005.02.065 |
| Citation | McMullen MR, et al. (2005) Early growth response-1 transcription factor is essential for ethanol-induced fatty liver injury in mice. Gastroenterology 128(7):2066-76 |
| abstractText | BACKGROUND & AIMS: Early growth response-1 (Egr-1), an immediate early gene/zinc-finger transcription factor, is required for maximal stimulation of tumor necrosis factor alpha (TNF-alpha) transcription in response to lipopolysaccharide (LPS). Because chronic ethanol exposure sensitizes macrophages to LPS-stimulated TNF-alpha expression, we have investigated the role of Egr-1 in mediating increased LPS-stimulated TNF-alpha expression after chronic ethanol feeding. Furthermore, because TNF-alpha contributes to alcoholic liver injury, we tested the hypothesis that Egr-1 is required for the development of ethanol-induced fatty liver injury in wild type and egr-1 -/- mice. METHODS: Wild-type and egr-1 -/- mice were fed ethanol-containing diets or pair-fed control diets for 6 weeks. RESULTS: Wild-type mice fed the ethanol diet developed hepatic steatosis characterized by micro- and macrovesicular lipid accumulation. However, egr-1 -/- mice did not develop steatosis after ethanol feeding. Alanine transferase and TNF-alpha concentrations in serum were increased after ethanol feeding in wild-type but not egr-1 -/- mice. In wild-type mice, challenge with LPS increased Egr-1 messenger RNA (mRNA) and DNA binding activity in liver; this response to LPS was enhanced after chronic ethanol feeding. LPS challenge also increased hepatic TNF-alpha mRNA and serum TNF-alpha to a greater extent after ethanol feeding compared with pair-fed wild-type mice. However, chronic ethanol feeding did not enhance LPS-stimulated TNF-alpha mRNA or serum TNF-alpha in egr-1 -/- mice. CONCLUSIONS: These data show that Egr-1 contributes to increased LPS-mediated TNF-alpha expression after chronic ethanol and that the absence of Egr-1 prevents chronic ethanol-induced fatty liver, as well as increased sensitivity to LPS. |
