TGF-beta1 reduces the heterogeneity of astrocytic cyclooxygenase-2 and nitric oxide synthase-2 gene expression in a stimulus-independent manner.
Transforming growth factor-beta1 (TGF-beta1) 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-beta1 is dependent upon changes in gene expression. Recently, we demonstrated that TGF-beta1 enhances astrocytic nitric oxide production induced by lipopolysaccharide (LPS) plus interferon-gamma (IFNgamma) 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-beta1 on another pro-inflammatory gene, cyclooxygenase-2 (COX-2); and (2) to assess stimulus specificity. We found that TGF-beta1 augmented LPS plus IFNgamma-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-beta1 enhanced the number of astrocytes that expressed both COX-2 and NOS-2 protein when either IL-1beta or TNFalpha was used in lieu of LPS. Collectively, these results suggest that TGF-beta1 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.
Hamby
Mary E
ME
Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030, USA.
Hewett
James A
JA
Hewett
Sandra J
SJ
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1 / Q000502:physiology*
D008070:Lipopolysaccharides; D053773:Transforming Growth Factor beta1; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2