Hypoxia suppresses the production of matrix metalloproteinases and the migration of humanmonocyte‐derived dendritic cells
Hypoxia suppresses the production of matrix metalloproteinases and the migration of humanmonocyte‐derived dendritic cells
复制标题
DOI：
10.1002/eji.200526262
复制
发表时间：
2005-12
影响因子：
5.4
通讯作者：
Wenli Zhao;S. Darmanin;Q. Fu;Jian Chen;Hongyan Cui;Jingxin Wang;F. Okada;J. Hamada;Y. Hattori;T. Kondo;J. Hamuro;M. Asaka;Masanobu Kobayashi
中科院分区：
文献类型：
--
作者：
Wenli Zhao;S. Darmanin;Q. Fu;Jian Chen;Hongyan Cui;Jingxin Wang;F. Okada;J. Hamada;Y. Hattori;T. Kondo;J. Hamuro;M. Asaka;Masanobu Kobayashi
由于大多数实体瘤是缺氧的，因此实体瘤中的树突状细胞（DC）也暴露于缺氧。虽然肿瘤细胞对缺氧的许多适应性反应是已知的，但尚不确定缺氧如何影响DC的功能。为探讨缺氧对DC功能的影响，我们比较了缺氧和常氧条件下分化的人单核细胞来源的DC（hmDC）表面标志物、细胞因子、趋化因子受体和基质金属蛋白酶（MMP）的表达。两组hmDC表达相似水平的表面标志物和细胞因子。然而，MMP-9和膜型-1-MMP的表达，以及迁移活性，在缺氧条件下分化的hmDC与常氧对应物相比，受到显著抑制。我们还证明了在缺氧条件下，hmDC中的MMP-9的产生恢复。总的来说，我们的研究结果表明，缺氧微环境抑制MMP的产生hmDC，最有可能通过脱乙酰化的MMP启动子区域，从而抑制hmDC的迁移活性。我们的研究结果表明，实体瘤组织中的缺氧微环境可能抑制DC的功能。
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.