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Hypoxia suppresses the production of matrix metalloproteinases and migration of human monocyte-derived dendritic cells

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Title: Hypoxia suppresses the production of matrix metalloproteinases and migration of human monocyte-derived dendritic cells
Authors: Zhao, Wenli Browse this author
Darmanin, Stephanie Browse this author
Fu, Qiang Browse this author
Chen, Jian Browse this author
Cui, Hongyan Browse this author
Wang, Jingxin Browse this author
Okada, Futoshi Browse this author
Hamada, Jun-ichi Browse this author
Hattori, Yuu-ichi Browse this author
Kondo, Takeshi Browse this author →KAKEN DB
Hamuro, Junji Browse this author
Asaka, Masahiro Browse this author →KAKEN DB
Kobayashi, Masanobu13 Browse this author
Authors(alt): 小林, 正伸13
Keywords: Dendritic cell
Hypoxia
Matrix metalloproteinase
Migration
Issue Date: 31-Dec-2005
Publisher: WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Journal Title: European Journal of Immunology
Volume: 35
Issue: 12
Start Page: 3468
End Page: 3477
Publisher DOI: 10.1002/eji.200526262
PMID: 16259004
Abstract: As most solid tumors are hypoxic, dendritic cells (DC) in solid tumors are also exposed to hypoxia. While many adaptation responses of tumor cells to hypoxia are known, it is yet to be determined how hypoxia affects the functions of DC. To explore the effects of hypoxia on the functions of DC, we compared the expression of surface markers, cytokines, chemokine receptors and matrix metalloproteinases (MMP) of human monocyte-derived DC (hmDC) differentiated under hypoxia to those differentiated under normoxia. Both groups of hmDC expressed similar levels of surface markers and cytokines. However, expression of MMP-9 and membrane type-1-MMP, as well as migrating activity, was significantly suppressed in hmDC differentiated under hypoxia compared with their normoxia counterparts. We also demonstrated that trichostatin A restored the production of MMP-9 in hmDC, under hypoxia. Collectively, our findings show that a hypoxic microenvironment suppresses the production of MMP in hmDC, most probably through the deacetylation of promoter regions of MMP, thus suppressing the migrating activity of hmDC. Our results suggest that the hypoxic microenvironment in solid tumor tissues may suppress the function of DC
Relation: http://www.interscience.wiley.com/
Type: article (author version)
URI: http://hdl.handle.net/2115/988
Appears in Collections:遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 小林 正伸

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