Induction of the α1-antichymotrypsin gene in the brain associated with TGF-β1 deficiency or systemic administration of endotoxin

Hiroshi Saito, Leonard D. Shultz, Mala Sinha, John Papaconstantinou

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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.

Original languageEnglish
Pages (from-to)270-275
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number2
StatePublished - Sep 24 1999

Bibliographical note

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.).

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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