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.
Copyright © 2011 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Butadienes / pharmacology
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Cell Line
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Doxycycline / pharmacology*
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Epithelial Cells / drug effects
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Epithelial Cells / metabolism
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Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis*
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Granulocyte-Macrophage Colony-Stimulating Factor / genetics
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Interleukin-6 / biosynthesis*
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Interleukin-6 / genetics
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MAP Kinase Kinase 1 / antagonists & inhibitors
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MAP Kinase Kinase 1 / metabolism
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MAP Kinase Kinase 2 / antagonists & inhibitors
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MAP Kinase Kinase 2 / metabolism
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MAP Kinase Signaling System / drug effects*
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Mice
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / metabolism*
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Nitriles / pharmacology
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Phosphorylation / drug effects
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RNA, Messenger / genetics
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Sulfones / pharmacology
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Thymocytes / cytology
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Thymocytes / drug effects
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Thymocytes / metabolism
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Transcription Factor RelA / antagonists & inhibitors
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Transcription Factor RelA / metabolism
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Up-Regulation / drug effects
Substances
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3-(4-methylphenylsulfonyl)-2-propenenitrile
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Butadienes
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Interleukin-6
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NF-kappa B
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Nitriles
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RNA, Messenger
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Sulfones
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Transcription Factor RelA
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U 0126
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Granulocyte-Macrophage Colony-Stimulating Factor
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MAP Kinase Kinase 1
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MAP Kinase Kinase 2
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Map2k1 protein, mouse
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Map2k2 protein, mouse
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Doxycycline