Non-genomic action of TCDD to induce inflammatory responses in HepG2 human hepatoma cells and in liver of C57BL/6J mice

作者：Li Wen; Vogel Christoph F A; Wu Dalei; Matsumura Fumio^*

来源：Biological Chemistry, 2010, 391(10): 1205-1219.

DOI：10.1515/BC.2010.126

• AhR
• Cox-2
• HepG2 human hepatoma cells
• inflammatory responses
• liver of C57BL/6J mice
• non-genomic action
• SOCS3
• TCDD

To assess the significance of the non-genomic signaling of TCDD (=dioxin) on liver of C57BL/6 mice and HepG2 human hepatoma cells, we first determined the group of markers that are susceptible to inhibition by parthenolide, a compound known to specifically suppress NF-kappa B-mediated inflammation. Of those, the most consistent marker turned out to be SOCS3 (a suppressor of cytokine signaling) known to respond to inflammation. An early diagnostic test on the action of TCDD on HepG2 cells in vitro within 3-6 h indicated that Cox-2 and SOCS3 are mainly induced via a non-genomic route, whereas PAI-2 appears to be induced through the classical action route. More detailed diagnostic tests at later stages of action of TCDD in HepG2 cells revealed that induction of IL-1 beta, BAFF, and iNOS are largely mediated by the protein kinase-dependent non-genomic route. An in vivo study on the 7 day action of TCDD on liver of AhR(NLS) mice showed that several early markers (e. g., Cox-2, MCP-1 and SOCS3) are induced, but not late markers such as IL-1b. Together, these results show that the non-genomic pathway contributes significantly to the early stress response reactions to TCDD that includes inflammation in hepatoma cells as well as in the liver.

• 出版日期2010-10