Doxycycline up-regulates the expression of IL-6 and GM-CSF via MAPK/ERK and NF-κB pathways in mouse thymic epithelial cells

作者：Huang, Ying^*; Li, Rong; Chen, Xun; Zhuo, Ya; Jin, Rong; Qian, Xiao Ping; Jiang, Yan Qiu; Zeng, Zi Han; Zhang, Yu; Shao, Qi Xiang

来源：International Immunopharmacology, 2011, 11(9): 1143-1149.

DOI：10.1016/j.intimp.2011.03.011

• Doxycycline
• Thymic epithelial cells
• Cytokine
• MAPK
• NF-kappa B

Thymic epithelial cells (TECs) constitute a major component of the thymic stroma which provides a microenvironment critical for developing thymocytes. We have previously demonstrated that doxycycline (Dox), a tetracycline derivative, enhances the proliferation of the mouse thymic epithelial cell line 1 (MTEC1) via MAPK/ERK signal pathway. Herein we provide evidence that Dox also has profound impact on the cytokine production by MTEC1. Specifically, the expression of IL-6 and GM-CSF, both at mRNA and protein levels, was found to be increased in a time- and dose-dependent manner with the addition of Dox. Western blotting analysis revealed that treatment with Dox-induced phosphorylation of the p65 subunit of NF-kappa B and ERK. Notably, Dox-induced up-regulation of IL-6 and GM-CSF was largely abolished after pretreatment of MTEC1 with either NF-kappa B inhibitor BAY11-7082 or MEK1/2 inhibitor U0126, supporting the involvement of the two pathways in the process. These findings warrant further investigation into the potential application of Dox in T-cell reconstitution in such situations as chemotherapy, radiotherapy, bone marrow transplantation and HIV infection.

• 出版日期2011-9
• 单位江苏大学; 北京大学; 南昌大学