TGF-β1 potentiates astrocytic nitric oxide production by expanding the population of astrocytes that express NOS-2

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Both transforming growth factor-β1 (TGF-β1) and nitric oxide synthase-2 (NOS-2) are upregulated under various neuropathological states. Evidence suggests that TGF-β1 can either attenuate or augment NOS-2 expression, with the prevailing effect dependent on the experimental paradigm employed and the cell-type under study. The purpose of the present study was to determine the effect of TGF-β1 on astrocytic NOS-2 expression. In purified astrocyte cultures, TGF-β1 alone did not induce NOS-2 or NO production. However, NO production induced by lipopolysaccharide (LPS) plus IFNγ was enhanced by TGF-β1 in a concentration-dependent manner between 10 and 1,000 pg/mL. The presence of IFNγ was not necessary for this effect to occur, as TGF-β1 enhanced NO production induced by LPS in a similar fashion. In cultures stimulated with LPS plus IFNγ, the enhancement of NO production by TGF-β1 was associated with a corresponding increase in NOS-2 mRNA and protein expression. Interestingly, immunocytochemical assessment of NOS-2 protein expression demonstrated that TGF-β1 augmented astrocytic NO production, specifically by increasing the pool of astrocytes capable of expressing NOS-2 induced by either LPS (∼threefold) or LPS plus IFNγ (∼sevenfold). In a broader sense, our results suggest that TGF-β1 recruits a latent population of astrocytes to respond to stimulation by pro-inflammatory mediators.

Original languageEnglish (US)
Pages (from-to)566-577
Number of pages12
JournalGLIA
Volume54
Issue number6
DOIs
StatePublished - Nov 1 2006
Externally publishedYes

Keywords

  • Heterogeneity
  • IFNγ
  • LPS
  • Microglia
  • Transcription
  • Transforming growth factor
  • iNOS

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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