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

Reiko Kuno, Yusuke Yoshida, Atsumi Nitta, Toshitaka Nabeshima, Jinyan Wang, Yoshifumi Sonobe, Jun Kawanokuchi, Hideyuki Takeuchi, Tetsuya Mizuno, Akio Suzumura

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108 Citations (Scopus)


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-α (TNF-α)-induced production of neurotrophic factors. We show here that cultured astrocytes express both TNF-α receptor 1 (TNFR1) and TNFR2, and that activation of these receptors by TNF-α promotes expression of both NGF and GDNF. In addition, we observe that not only exogenous TNF-α but also TNF-α produced by astrocytes induce NGF and GDNF production in astrocytes. These results suggest that an autocrine loop involving TNF-α contributes to the production of neurotrophic factors in response to inflammation.

Original languageEnglish
Pages (from-to)12-18
Number of pages7
JournalBrain Research
Issue number1
Publication statusPublished - 20-10-2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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