Selective regulation of growth factor expression in cultured cortical astrocytes by neuro-pathological toxins

Astrocytes are integrated in the complex regulation of neurodegeneration and neuronal damage in the CNS. It is well-known that astroglia produces a plethora of growth factors which might be protective for neurons. Growth factors prevent neurons from cell death and promote proliferation and differentiation of precursor cells. Previous data suggest that astrocytes may respond to toxic stimuli by a selective mobilization of guarding molecules. In the present study, we have investigated the potency of different pathological stimuli such as lipopolysaccharides, tumor necrosis factor alpha, glutamate, and hydrogen peroxide to activate cultured cortical astroglia and stimulate growth factor expression. Astroglial cultures were exposed to the above factors for 24h at non-toxic concentrations for astrocytes. Growth factor expression was analyzed by real-time PCR, oligo-microarray technique, and ELISA. Insulin-like growth factor-1 was selectively down-regulated by lipopolysaccharides and tumor necrosis factor alpha, bone morphogenetic protein 6 by all stimuli. In contrast, lipopolysaccharides, tumor necrosis factor alpha, and glutamate increased leukemia inhibitory factor. Fibroblast growth factor 2 was up-regulated by lipopolysaccharides and tumor necrosis factor alpha and down-regulated by hydrogen peroxide. Besides hydrogen peroxide, all other stimuli promoted vascular epithelial growth factor A mRNA and protein expression. It appears that lipopolysaccharides but not tumor necrosis factor alpha effects on vascular epithelial growth factor A depend on the classic NFkappaB pathway. Our data clearly demonstrate that astroglia actively responses to diverse pathological compounds by a selective expression pattern of growth factors. These findings make astrocytes likely candidates to participate in disease-specific characteristics of neuronal support or damage.