PMID- 9645958
OWN - NLM
STAT- MEDLINE
DCOM- 19981009
LR  - 20190826
IS  - 0169-328X (Print)
IS  - 0169-328X (Linking)
VI  - 55
IP  - 1
DP  - 1998 Mar 30
TI  - Enhancement of beta-amyloid precursor protein transcription and expression by the 
      soluble interleukin-6 receptor/interleukin-6 complex.
PG  - 35-44
AB  - 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.
FAU - Ringheim, G E
AU  - Ringheim GE
AD  - Hoechst Marion Roussel, Neuroscience Disease Group, Bridgewater, NJ 08807-0800, 
      USA. ringheil@brwhcc3.hcc.com
FAU - Szczepanik, A M
AU  - Szczepanik AM
FAU - Petko, W
AU  - Petko W
FAU - Burgher, K L
AU  - Burgher KL
FAU - Zhu, S Z
AU  - Zhu SZ
FAU - Chao, C C
AU  - Chao CC
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Brain Res Mol Brain Res
JT  - Brain research. Molecular brain research
JID - 8908640
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Antigens, CD)
RN  - 0 (Fetal Proteins)
RN  - 0 (IL6ST protein, human)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Interleukin-6)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 133483-10-0 (Cytokine Receptor gp130)
RN  - EC 1.13.12.- (Luciferases)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Alzheimer Disease/genetics/metabolism
MH  - Amino Acid Sequence
MH  - Amyloid beta-Protein Precursor/*biosynthesis/genetics
MH  - Antigens, CD/biosynthesis/genetics
MH  - Base Sequence
MH  - Brain/cytology/embryology/*metabolism
MH  - Cytokine Receptor gp130
MH  - Fetal Proteins/biosynthesis/genetics
MH  - Fibroblast Growth Factor 2/pharmacology
MH  - Gene Expression Regulation/*drug effects
MH  - Genes, Reporter
MH  - Humans
MH  - Interleukin-6/*pharmacology
MH  - Lipopolysaccharides/pharmacology
MH  - Luciferases/biosynthesis
MH  - Membrane Glycoproteins/biosynthesis/genetics
MH  - Molecular Sequence Data
MH  - Neoplasm Proteins/biosynthesis/genetics
MH  - Neuroblastoma/pathology
MH  - Neurons/drug effects/metabolism
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Receptors, Interleukin-6/biosynthesis/genetics/*physiology
MH  - Recombinant Fusion Proteins/biosynthesis
MH  - Solubility
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Transcription, Genetic/*drug effects
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 1998/07/01 00:00
MHDA- 1998/07/01 00:01
CRDT- 1998/07/01 00:00
PHST- 1998/07/01 00:00 [pubmed]
PHST- 1998/07/01 00:01 [medline]
PHST- 1998/07/01 00:00 [entrez]
AID - S0169328X97003562 [pii]
AID - 10.1016/s0169-328x(97)00356-2 [doi]
PST - ppublish
SO  - Brain Res Mol Brain Res. 1998 Mar 30;55(1):35-44. doi: 
      10.1016/s0169-328x(97)00356-2.