TGF-β1 reduces the heterogeneity of astrocytic cyclooxygenase-2 and nitric oxide synthase-2 gene expression in a stimulus-independent manner

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Transforming growth factor-β1 (TGF-β1) is upregulated by inflammatory mediators in several neurological diseases/disorders where it either participates in the pathology or provides protection. Often, the biological outcome of TGF-β1 is dependent upon changes in gene expression. Recently, we demonstrated that TGF-β1 enhances astrocytic nitric oxide production induced by lipopolysaccharide (LPS) plus interferon-γ (IFNγ) by increasing the number of astrocytes in a population that express NOS-2. The purpose of this study was twofold: (1) to determine whether this effect occurs more generally by assessing the effect of TGF-β1 on another pro-inflammatory gene, cyclooxygenase-2 (COX-2); and (2) to assess stimulus specificity. We found that TGF-β1 augmented LPS plus IFNγ-induced COX-2 mRNA and protein expression, by nearly tripling the number of astrocytes that express COX-2. The effect was not stimulus-specific as TGF-β1 enhanced the number of astrocytes that expressed both COX-2 and NOS-2 protein when either IL-1β or TNFα was used in lieu of LPS. Collectively, these results suggest that TGF-β1 augments overall protein expression levels of select pro-inflammatory genes in astrocytes in a promiscuous manner by reducing the magnitude of noise in the cellular population.

Original languageEnglish (US)
Pages (from-to)115-124
Number of pages10
JournalProstaglandins and Other Lipid Mediators
Volume85
Issue number3-4
DOIs
StatePublished - Mar 2008

Keywords

  • Astrocytes
  • COX-2
  • Heterogeneity
  • IFNγ
  • IL-1β
  • LPS
  • NOS-2
  • Nitric oxide
  • PGE
  • TNF-α

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Pharmacology
  • Cell Biology

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