論文 - 詳細
| RRC ID | 62725 |
|---|---|
| 著者 | Gong FY, Deng JY, Shi YF. |
| タイトル | Mek and p38 MAPK-dependant pathways are involoved in the positive effect of interleukin-6 on human growth hormone gene expression in rat MtT/S somatotroph cells. |
| ジャーナル | Chin Med Sci J |
| Abstract |
OBJECTIVE:To investigate the effect of interleukin-6 (IL-6) on the human growth hormone (hGH) gene expression in a rat somatotropic pituitary cell line MtT/S. METHODS:The plasmids containing various lengths of hGH gene 5'-promoter fragments were constructed. Stably transfected MtT/S cells were created by cotransfecting the above plasmids and pcDNA3. 1(+) with DMRIE-C transfection reagent After the administration of these cells with IL-6 and/or various inhibitors of signaling transduction pathways, the luciferase activities in MtT/S cells lysis were assayed to demonstrate the effects of IL-6 on hGH gene promoter activity and possibly involved mechanism. RESULTS:The 10(3) U/mL IL-6 stimulated GH secretion and synthesis, and promoted the 5'-promoter activity of GH gene in stably transfected MtT/SGL cells with the action of 1.69 times above the control. Among inhibitors of signaling transduction pathways, mitogen-activated protein kinase kinase (MAPKK/MEK) inhibitor PD98059 (40 micromol/L) and p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 (5 micromol/L) completely blocked the stimulatory effect of IL-6. Western blot analysis further confirmed the activation of phosphorylated MEK and p38 MAPK in MtT/SGL cells. Neither over-expression of Pit-1 nor inhibition of Pit-1 expression affected IL-6 induction of hGH promoter activity. A series of deletion constructs of hGH promoter were created to identify the DNA sequence that mediated the effect of IL-6. The results showed that the stimulatory effect of IL-6 was abolished following deletion of the -196 to - 132 bp fragment. CONCLUSIONS:IL-6 promotes GH secretion and synthesis by rat MtT/S somatotroph cells. The stimulatory effect of IL-6 on hGH gene promoter appears to require the activation of MEK and p38 MAPK, and a fragment of promoter sequence that spans the - 196 to - 132 bp of the gene, but may be unlinked with Pit-1 protein. |
| 巻・号 | 23(2) |
| ページ | 73-80 |
| 公開日 | 2008-6-1 |
| DOI | 10.1016/s1001-9294(09)60016-x |
| PMID | 18686625 |
| MeSH | Animals Cell Line Gene Expression Regulation Human Growth Hormone* / genetics Human Growth Hormone* / metabolism Humans Interleukin-6 / genetics Interleukin-6 / metabolism* JNK Mitogen-Activated Protein Kinases / genetics JNK Mitogen-Activated Protein Kinases / metabolism* MAP Kinase Signaling System / physiology* Mitogen-Activated Protein Kinase Kinases / genetics Mitogen-Activated Protein Kinase Kinases / metabolism* Promoter Regions, Genetic Rats Somatotrophs / cytology Somatotrophs / metabolism* p38 Mitogen-Activated Protein Kinases / genetics p38 Mitogen-Activated Protein Kinases / metabolism* |
| リソース情報 | |
| ヒト・動物細胞 | MtT/S(RCB0528) |