Kuno Reiko, Yoshida Yusuke, Nitta Atsumi, Nabeshima Toshitaka, Wang Jinyan, Sonobe Yoshifumi, Kawanokuchi Jun, Takeuchi Hideyuki, Mizuno Tetsuya, Suzumura Akio
Department of Neuroimmunology, Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
Brain Res. 2006 Oct 20;1116(1):12-8. doi: 10.1016/j.brainres.2006.07.120. Epub 2006 Sep 7.
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.
神经营养因子，即神经生长因子（NGF）和胶质细胞系源性神经营养因子（GDNF），由星形胶质细胞产生，并由包括细菌脂多糖和促炎细胞因子在内的炎症刺激所诱导。在本研究中，我们检测了肿瘤坏死因子-α（TNF-α）诱导神经营养因子产生的调控机制。我们在此表明，培养的星形胶质细胞表达TNF-α受体1（TNFR1）和TNFR2，并且TNF-α对这些受体的激活促进了NGF和GDNF的表达。此外，我们观察到，不仅外源性TNF-α，而且星形胶质细胞产生的TNF-α也能诱导星形胶质细胞中NGF和GDNF的产生。这些结果表明，涉及TNF-α的自分泌环有助于在炎症反应中产生神经营养因子。
