Induction of the alpha(1)-antichymotrypsin gene in the brain associated with TGF-beta1 deficiency or systemic administration of endotoxin.
We report that mRNA levels for alpha(1)-antichymotrypsin (ACT), a component of beta-amyloid plaques in Alzheimer's disease, are significantly increased in the brains of two different mouse models that develop inflammation: (1) acute inflammation caused by intraperitoneal injection with lipopolysaccharide (LPS) and (2) chronic inflammation in knockout mice lacking the anti-inflammatory cytokine transforming growth factor beta1 (TGF-beta1). While brain mRNA levels for the inflammatory cytokines TNFalpha, IL-1beta, and IL-6 were all elevated in the LPS-injected mice, only the mRNA for IL-1beta increased significantly in TGF-beta1-deficient mice. The transcription factor C/EBPbeta was strongly activated in the brains of both models. These results support the hypothesis that, through induction of the ACT gene in the brain, inflammation plays an important role during the development of Alzheimer's disease and that IL-1beta and C/EBPbeta may be involved in this process.
Saito
H
H
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, Texas, 77555-0643, USA. hsaito@utmb.edu
Shultz
L D
LD
Sinha
M
M
Papaconstantinou
J
J
D000818:Animals; D001921:Brain / Q000378:metabolism*; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation; D007249:Inflammation; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008817:Mice, Mutant Strains; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000172:deficiency* / Q000235:genetics; D000514:alpha 1-Antichymotrypsin / Q000096:biosynthesis / Q000235:genetics*
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009687:Nuclear Proteins; D016212:Transforming Growth Factor beta; D000514:alpha 1-Antichymotrypsin