Neurochemical Research

, Volume 40, Issue 6, pp 1220–1231 | Cite as

Critical Role of TAK1-Dependent Nuclear Factor-κB Signaling in 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced Astrocyte Activation and Subsequent Neuronal Death

  • Chunhua Wan
  • Yang Zhang
  • Junkang Jiang
  • Shengyang Jiang
  • Xiaoke Nie
  • Aihong Li
  • Aisong Guo
  • Qiyun Wu
Original Paper


2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been recently shown to elicit inflammatory response in a number of cell-types. However, whether TCDD could provoke inflammation in astrocytes, the most abundant glial cells in central nervous system (CNS), remains virtually unknown. In the present study, we showed that TCDD exposure could induce evident astrocyte activation both in vivo and in vitro. Further, we found that TGF-β-activated kinase 1 (TAK1), a critical regulator of NF-κB signaling, was rapidly phosphorylated in the process of TCDD-induced reactive astroglia. Exposure to TCDD led to rapid TAK1 and NF-κB p65 phosphorylation, as well as IKBα degradation. Moreover, blockage of TAK1 using siRNA oligos or TAK1 inhibitor 5Z-7-oxozeaenol significantly attenuated TCDD-induced astrocyte activation as well as the release of TNF-α. Finally, we showed that the conditioned medium of TCDD-treated astrocytes promoted the apoptosis of PC12 neuronal cells, which could be blocked with the pre-treatment of TAK1 inhibitor. Taken together, these findings suggested that TCDD could promote the inflammatory activation of astrocytes through modulating TAK1-NF-κB cascade, implicating that reactive astrocytes might contribute to TCDD-induced adverse effects on CNS system.


TCDD TAK1 Activation Astrocytes NF-κB 





Aryl hydrocarbon receptor


Aryl hydrocarbon receptor nuclear translocator


Central nervous system


TGF-β activated kinase 1


Astrocyte conditioned medium


Glial fibrillary acidic protein



This work was supported by the National Natural Science Foundation of China (Nos. 21477058, 21077061 and 21277078), and a project funded by the Natural Science Foundation of the Jiangsu Higher Education Institutions (No. 13KJB330006).

Conflict of interest

The authors declare no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Chunhua Wan
    • 1
  • Yang Zhang
    • 1
  • Junkang Jiang
    • 1
  • Shengyang Jiang
    • 1
  • Xiaoke Nie
    • 1
  • Aihong Li
    • 2
  • Aisong Guo
    • 2
  • Qiyun Wu
    • 1
  1. 1.Department of Nutrition and Food Hygieney, School of Public HealthNantong UniversityNantongPeople’s Republic of China
  2. 2.Department of NeurologyAffiliated Hospital of Nantong UniversityNantongPeople’s Republic of China

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