The role of TNF-alpha and its receptors in the production of NGF and GDNF by astrocytes

The neurotrophic factors, nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF), are produced by astrocytes, and are induced by inflammatory stimuli including bacterial lipopolysaccharide and pro-inflammatory cytokines. In this study, we examined the regulatory mechanisms of tumor necrosis factor-alpha (TNF-alpha)-induced production of neurotrophic factors. We show here that cultured astrocytes express both TNF-alpha receptor 1 (TNFR1) and TNFR2, and that activation of these receptors by TNF-alpha promotes expression of both NGF and GDNF. In addition, we observe that not only exogenous TNF-alpha but also TNF-alpha produced by astrocytes induce NGF and GDNF production in astrocytes. These results suggest that an autocrine loop involving TNF-alpha contributes to the production of neurotrophic factors in response to inflammation. (c) 2006 Elsevier B.V. All rights reserved.