title: Doxycycline up-regulates the expression of IL-6 and GM-CSF via MAPK/ERK and NF-κB pathways in mouse thymic epithelial cells.
abstract: 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-κB and ERK. Notably, Dox-induced up-regulation of IL-6 and GM-CSF was largely abolished after pretreatment of MTEC1 with either NF-κB 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.
authors: Department of Immunology, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, PR China. huangying007@yeah.net
authors: Ying
authors: Y
authors: Huang
authors: Rong
authors: R
authors: Li
authors: Xun
authors: X
authors: Chen
authors: Ya
authors: Y
authors: Zhuo
authors: Rong
authors: R
authors: Jin
authors: Xiao Ping
authors: XP
authors: Qian
authors: Yan Qiu
authors: YQ
authors: Jiang
authors: Zi Han
authors: ZH
authors: Zeng
authors: Yu
authors: Y
authors: Zhang
authors: Qi Xiang
authors: QX
authors: Shao
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D004318:Doxycycline / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048370:MAP Kinase Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D013450:Sulfones / Q000494:pharmacology; D060168:Thymocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D002070:Butadienes; D015850:Interleukin-6; D016328:NF-kappa B; D009570:Nitriles; D012333:RNA, Messenger; D013450:Sulfones; D051996:Transcription Factor RelA; C113580:U 0126; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482127:Map2k1 protein, mouse; C482129:Map2k2 protein, mouse; D004318:Doxycycline