1. Главная
  2. Ресурсы
  3. Библиотечный поиск
Interleukin-6inhibits growthhormone-mediated geneexpression inhepatocytes Tamer A. AhmedMark D. BuzzelliCharles H. Lang2007 год

Interleukin-6 inhibits growth hormone-mediated gene expression in hepatocytes
статья из журнала

Страница публикацииПубликация в OpenAlex
Аннотация: During systemic inflammation, the liver becomes unresponsive to growth hormone (GH), resulting in decreased plasma insulin-like growth factor-I (IGF-I) with concomitant reductions in lean body mass. Transgenic mice that overexpress IL-6 also demonstrate impaired growth and decreased IGF-I. To determine whether IL-6 directly inhibits GH-inducible gene expression, CWSV-1 hepatocytes were incubated with IL-6 (10 ng/ml), then stimulated with recombinant human GH (500 ng/ml, 18 h). The increase in IGF-I and serine protease inhibitor 2.1 (Spi 2.1) mRNA in GH-treated cells was inhibited by treatment with IL-6 for 24 h. To investigate potential mechanisms, we examined the effects of IL-6 on GH receptor (GHR) expression and GH signaling via the JAK/signal transducer and activator of transcription (STAT) and MAP kinase pathways. Incubation of cells with IL-6 (10 ng/ml, 24 h) had no effect on GHR abundance or signaling proteins JAK2, STAT5b, and ERK1/2. Although GH transiently increased (2- to 5-fold) the tyrosine phosphorylation of GHR, JAK2, STAT5b, and ERK1/2, IL-6 did not alter these phosphorylation events. However, nuclear protein from IL-6-treated cells demonstrated reduced STAT5 DNA binding (by EMSA) at 15 min (-20%) and 60 min (-43%) after GH stimulation. To determine whether IL-6 inhibits GH-inducible promoter activity, CWSV-1 cells were transfected with Spi 2.1 or prolactin receptor promoter luciferase vectors, incubated with or without IL-6, then stimulated with GH. The induction of both Spi 2.1 (7.5-fold) and prolactin receptor (4-fold) promoter activity by GH was inhibited by IL-6. In summary, IL-6 mediates hepatic GH resistance by a time-dependent inhibition of GH-inducible promoter activity that is associated with reductions in STAT5 DNA binding.
Год издания: 2007
Авторы: Tamer A. Ahmed, Mark D. Buzzelli, Charles H. Lang, John B. Capen, Margaret L. Shumate, Maithili Navaratnarajah, Murali Nagarajan, Robert N. Cooney
Издательство: American Physiological Society
Источник: AJP Gastrointestinal and Liver Physiology
Ключевые слова: Growth Hormone and Insulin-like Growth Factors, Liver Disease Diagnosis and Treatment, Lipid metabolism and disorders
Другие ссылки: AJP Gastrointestinal and Liver Physiology (HTML)
PubMed (HTML)