TY - JOUR
T1 - Induction of the α1-antichymotrypsin gene in the brain associated with TGF-β1 deficiency or systemic administration of endotoxin
AU - Saito, Hiroshi
AU - Shultz, Leonard D.
AU - Sinha, Mala
AU - Papaconstantinou, John
N1 - Funding Information:
We thank Drs. S. L. McKnight and M. H. Morales for providing the cDNA clones for C/EBPs and ACT, respectively, and Dr. D. A. Konkel for critically reading the manuscript. This work was supported by the following grants: John Sealy Memorial Endowment Fund for Biomedical Research and P01 AG10514 from the National Institute on Aging (to J.P.), R01 CA20408 from the National Cancer Institute (to L.D.S.), Grant-in-Aid 97G-654 from the American Heart Association Texas Affiliate, and Seed Money from the Sealy Center on Aging, University of Texas Medical Branch (to H.S.).
PY - 1999/9/24
Y1 - 1999/9/24
N2 - We report that mRNA levels for α1-antichymotrypsin (ACT), a component of β-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 β1 (TGF-β1). While brain mRNA levels for the inflammatory cytokines TNFα, IL-1β, and IL-6 were all elevated in the LPS-injected mice, only the mRNA for IL-1β increased significantly in TGF-β1-deficient mice. The transcription factor C/EBPβ 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-1β and C/EBPβ may be involved in this process.
AB - We report that mRNA levels for α1-antichymotrypsin (ACT), a component of β-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 β1 (TGF-β1). While brain mRNA levels for the inflammatory cytokines TNFα, IL-1β, and IL-6 were all elevated in the LPS-injected mice, only the mRNA for IL-1β increased significantly in TGF-β1-deficient mice. The transcription factor C/EBPβ 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-1β and C/EBPβ may be involved in this process.
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U2 - 10.1006/bbrc.1999.1373
DO - 10.1006/bbrc.1999.1373
M3 - Article
C2 - 10491283
AN - SCOPUS:0033600709
SN - 0006-291X
VL - 263
SP - 270
EP - 275
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -