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

✍ Scribed by Mary E. Hamby; James A. Hewett; Sandra J. Hewett

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 830 KB
• Volume: 54
• Category: Article
• ISSN: 0894-1491
• DOI: 10.1002/glia.20411

✦ Synopsis

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. © 2006 Wiley‐Liss, Inc.