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

Abstract

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.

• Authors: Reiko Kuno, Yusuke Yoshida, Atsumi Nitta, Toshitaka Nabeshima, Jinyan Wang, Yoshifumi Sonobe, Jun Kawanokuchi, Hideyuki Takeuchi, Tetsuya Mizuno, Akio Suzumura
• Journal: Brain research (Brain Res) Vol. 1116 Issue 1 Pg. 12-8 (Oct 20 2006) ISSN: 0006-8993 [Print] Netherlands
• PMID: 16956589 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Blocking
• Glial Cell Line-Derived Neurotrophic Factor
• Lipopolysaccharides
• Nerve Growth Factors
• RNA, Messenger
• Receptors, Tumor Necrosis Factor
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Animals, Newborn
• Antibodies, Blocking (pharmacology)
• Astrocytes (drug effects, metabolism)
• Flow Cytometry
• Glial Cell Line-Derived Neurotrophic Factor (biosynthesis)
• Immunoenzyme Techniques
• Lipopolysaccharides (pharmacology)
• Mice
• Mice, Inbred C57BL
• Nerve Growth Factors (biosynthesis)
• RNA, Messenger (biosynthesis)
• Receptors, Tumor Necrosis Factor (antagonists & inhibitors, physiology)
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Necrosis Factor-alpha (pharmacology, physiology)