PMID- 8892349
OWN - NLM
STAT- MEDLINE
DCOM- 19970218
LR  - 20190909
IS  - 0197-4580 (Print)
IS  - 1558-1497 (Electronic)
IS  - 0197-4580 (Linking)
VI  - 17
IP  - 5
DP  - 1996 Sep-Oct
TI  - In vivo and in vitro evidence supporting a role for the inflammatory cytokine 
      interleukin-1 as a driving force in Alzheimer pathogenesis.
PG  - 761-6
AB  - Interleukin-1 (IL-1), an inflammatory cytokine overexpressed in the neuritic 
      plaques of Alzheimer's disease, activates astrocytes and enhances production and 
      processing of beta-amyloid precursor protein (beta-APP). Activated astrocytes, 
      overexpressing S100 beta, are a prominent feature of these neuritic plaques, and 
      the neurite growth-promoting properties of S100 beta have been implicated in the 
      formation of dystrophic neurites overexpressing beta-APP in neuritic plaques. 
      These facts collectively suggest that elevated levels of the inflammatory 
      cytokine IL-1 drive S100 beta and beta-APP overexpression and dystrophic neurite 
      formation in Alzheimer's disease. To more directly assess this driver potential 
      for IL-1, we analyzed IL-1 induction of S100 beta expression in vivo and in 
      vitro, and of beta-APP expression in vivo. Synthetic IL-1 beta was injected into 
      the right cerebral hemispheres of 13 rats. Nine additional rats were injected 
      with phosphate-buffered saline, and seven rats served as uninjected controls. The 
      number of astrocytes expressing detectable levels of S100 beta in tissue sections 
      from IL-1-injected brains was 1.5 fold that of either control group (p < 0.01), 
      while tissue S100 beta levels were approximately threefold that of controls (p < 
      0.05). The tissue levels of two beta-APP isoforms (approximately 130 and 135 kDa) 
      were also significantly elevated in IL-1-injected brains (p < 0.05). C6 glioma 
      cells, treated in vitro for 24 h with either IL-1 beta or IL-1 alpha, showed 
      significant increases in both S100 beta and S100 beta mRNA levels. These results 
      provide evidence that IL-1 upregulates both S100 beta and beta-APP expression, in 
      vivo and vitro, and support the idea that overexpression of IL-1 in Alzheimer's 
      disease drives astrocytic overexpression of S100 beta, favoring the growth of 
      dystrophic neurites necessary for evolution of diffuse amyloid deposits into 
      neuritic beta-amyloid plaques.
FAU - Sheng, J G
AU  - Sheng JG
AD  - Arkansas Children's Hospital Research Center, Department of Veterans' Affairs 
      Medical Center, Little Rock, AR, USA.
FAU - Ito, K
AU  - Ito K
FAU - Skinner, R D
AU  - Skinner RD
FAU - Mrak, R E
AU  - Mrak RE
FAU - Rovnaghi, C R
AU  - Rovnaghi CR
FAU - Van Eldik, L J
AU  - Van Eldik LJ
FAU - Griffin, W S
AU  - Griffin WS
LA  - eng
GR  - P01 AG012411/AG/NIA NIH HHS/United States
GR  - AG10208/AG/NIA NIH HHS/United States
GR  - AG12411/AG/NIA NIH HHS/United States
GR  - NS27414/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Neurobiol Aging
JT  - Neurobiology of aging
JID - 8100437
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Interleukin-1)
RN  - 0 (S100 Proteins)
SB  - IM
MH  - Alzheimer Disease/*pathology
MH  - Amyloid beta-Protein Precursor/biosynthesis
MH  - Animals
MH  - Astrocytes/metabolism
MH  - Blotting, Northern
MH  - Blotting, Western
MH  - Brain Chemistry/drug effects/physiology
MH  - Brain Neoplasms/metabolism
MH  - Glioma/metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - Interleukin-1/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - S100 Proteins/biosynthesis
MH  - Tumor Cells, Cultured
MH  - Up-Regulation/physiology
PMC - PMC3886636
MID - NIHMS542937
EDAT- 1996/09/01 00:00
MHDA- 1996/09/01 00:01
PMCR- 2014/01/09
CRDT- 1996/09/01 00:00
PHST- 1996/09/01 00:00 [pubmed]
PHST- 1996/09/01 00:01 [medline]
PHST- 1996/09/01 00:00 [entrez]
PHST- 2014/01/09 00:00 [pmc-release]
AID - S0197458096001042 [pii]
AID - 10.1016/0197-4580(96)00104-2 [doi]
PST - ppublish
SO  - Neurobiol Aging. 1996 Sep-Oct;17(5):761-6. doi: 10.1016/0197-4580(96)00104-2.