Brain capillary endothelial cells proliferate in response to NGF, express NGF receptors and secrete NGF after inflammation

Nerve growth factor (NGF) is an important factor regulating survival in development and during regenerative or neuroinflammatory processes. The aim of this study was to investigate whether brain capillary endothelial cells (BCEC) respond to NGF and whether pro-inflammatory substances induce the secretion of NGF in these cells. Cells were incubated with the growth factors NGF or vascular endothelial growth factor or endothelial cell growth factor, and proliferation was observed by incorporation of 5-bromo-2'-deoxy-uridine. NGF-secretion was measured by ELISA and expression of the NGF-receptors trkA and p75(NTR) by Western blot. Proliferation of BCEC was enhanced by exogenous NGF (1-100 ng/ml.). BCEC expressed NGF receptors in vivo (P3, P10, P20, adult) and displayed secretion of endogenous NGF ( approximately 20 pg/ml) into the medium. Treatment of BCEC with the proinflammatory cytokine interleukin-1beta+lipopolysaccharide enhanced expression of p75(NTR) and the secretion of NGF ( approximately 35 pg/ml). The effects of NGF were blocked by anti-NGF antibodies (5 microg/ml). In summary, NGF shows proliferative activity in BCEC, and NGF is secreted after inflammation. Therefore, the NGF pathway can modulate BCEC and may influence blood-brain barrier functions.