Enhancement of beta-amyloid precursor protein transcription and expression by the soluble interleukin-6 receptor/interleukin-6 complex
| Autor: | Kendra L. Burgher, Chun C Chao, Sheng Zu Zhu, Garth E. Ringheim, Ann Marie Szczepanik, Wayne Petko |
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| Rok vydání: | 1998 |
| Předmět: |
Fetal Proteins
Lipopolysaccharides Receptor complex Transcription Genetic Recombinant Fusion Proteins Protein subunit Molecular Sequence Data Biology Transfection Polymerase Chain Reaction Amyloid beta-Protein Precursor Neuroblastoma Cellular and Molecular Neuroscience Alzheimer Disease Antigens CD Genes Reporter Gene expression Cytokine Receptor gp130 Tumor Cells Cultured Amyloid precursor protein Humans Amino Acid Sequence RNA Messenger Luciferases Receptor Molecular Biology Neurons Messenger RNA Membrane Glycoproteins Base Sequence Interleukin-6 Brain Glycoprotein 130 Receptors Interleukin-6 Molecular biology Neoplasm Proteins Gene Expression Regulation Solubility Cell culture biology.protein Tetradecanoylphorbol Acetate Fibroblast Growth Factor 2 |
| Zdroj: | Molecular Brain Research. 55:35-44 |
| ISSN: | 0169-328X |
| DOI: | 10.1016/s0169-328x(97)00356-2 |
| Popis: | We investigated a potential role for the soluble interleukin-6 receptor (sIL-6R) in modulating interleukin-6 (IL-6) function in the central nervous system by assessing IL-6 and sIL-6R effects on beta-amyloid precursor protein (beta-APP) transcription and expression in cells of human neuronal origin. Cells transfected with a luciferase reporter plasmid containing a 3.8 kb DNA fragment of the beta-APP promoter were shown to have inducible promoter activity when treated with phorbol ester or basic fibroblast growth factor, but not when treated with lipopolysaccharide or Il-6. PCR amplification analysis revealed the presence of mRNA encoding the signaling subunit of the Il-6 receptor complex, the gp130 subunit, at levels approximating that found in human cortical tissue. The mRNA encoding the IL-6 receptor, however, was poorly expressed and was detectable only at high amplification cycles. When purified sIL-6R protein was added together with IL-6, there was a rapid induction of promoter activity within 2 h of stimulation followed by elevations in protein levels of both cell-associated and secreted beta-APP. Analysis of mRNA transcripts from human cortical brain tissue and cell cultures derived from fetal human brain demonstrated the presence of an alternatively spliced secreted form of the IL-6 receptor mRNA, suggesting that cells of the central nervous system may themselves be a source of sIL-6R protein. The capacity for sIL-6R to enhance IL-6 function and broaden the IL-6 target cell population in the brain has implications for the regulation of beta-APP expression in disease states such as Alzheimer's disease where elevations in brain IL-6 levels have been reported. |
| Databáze: | OpenAIRE |
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