Identification of an IL-6 response element in the human LCAT promoter
| Autor: | Brian R. Krause, Hilary A. Feister, Bruce Auerbach, Sotirios K. Karathanasis, Lisa A. Cole |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
biology
interleukin-6 Response element Reverse cholesterol transport Lipid metabolism QD415-436 Cell Biology Biochemistry Molecular biology STAT3 Endocrinology inflammation HDL cholesterol Transcription (biology) biology.protein Transcriptional regulation STAT protein Signal transduction transcription signal transduction |
| Zdroj: | Journal of Lipid Research, Vol 43, Iss 6, Pp 960-970 (2002) |
| ISSN: | 0022-2275 |
| DOI: | 10.1016/s0022-2275(20)30471-5 |
| Popis: | LCAT is a key enzyme of reverse cholesterol transport that is essential to maintain HDL-mediated lipid transport and cholesterol homeostasis. Alterations in LCAT expression have a profound effect on plasma HDL choles- terol concentrations. Previously LCAT mRNA and activity were shown to be regulated by several inflammatory cytok- ines, including the pleiotrophic cytokine interleukin-6 (IL-6). A series of full-length and sequential deletion LCAT pro- moter constructs were used to determine whether inflam- matory stimuli affect LCAT transcription and to further identify functional, cytokine-responsive promoter regions that mediate this response. Using transfected HepG2 cells, results indicate that treatment with IL-6 induced a 2.5-fold activation of full-length LCAT promoter activity. A minimal ( � 1514 bp to � 1508 bp) IL-6 response element with high sequence homology to the signal transducer and activator of transcription (STAT) family member, STAT3, was mapped within the distal promoter and shown to be sufficient to me- diate the IL-6 response. Further, overexpression of STAT3 significantly enhanced the effect of IL-6 on LCAT promoter activity. These data suggest that the IL-6 responsive tran- scription factor, STAT3, contributes to LCAT transcrip- tional regulation. The elucidation of distinct biochemical signaling pathways associated with inflammation may pro- vide new insight into transcriptional regulation of genes in- volved in lipid metabolism. —Feister, H. A., B. J. Auerbach, L. A. Cole, B. R. Krause, and S. K. Karathanasis. Identifica- tion of an IL-6 response element in the human LCAT pro- moter. J. Lipid Res. 2002. 43: 960-970. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|