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.
Kuno
Reiko
R
Department of Neuroimmunology, Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
Yoshida
Yusuke
Y
Nitta
Atsumi
A
Nabeshima
Toshitaka
T
Wang
Jinyan
J
Sonobe
Yoshifumi
Y
Kawanokuchi
Jun
J
Takeuchi
Hideyuki
H
Mizuno
Tetsuya
T
Suzumura
Akio
A
D000818:Animals; D000831:Animals, Newborn; D019138:Antibodies, Blocking / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000096:biosynthesis*; D007124:Immunoenzyme Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*
D019138:Antibodies, Blocking; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008070:Lipopolysaccharides; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha