Hypoxia inhibits the migratory capacity of human monocyte-derived dendritic cells.
Hypoxia, a prominent characteristic of inflammatory tissue lesions and solid tumour microenvironments, is a crucial stimulus capable of modulating the expression of specific genes involved in leucocyte recruitment. Although studies have shown that hypoxia can affect leucocyte migration by influencing the expression of migration-related genes, such as matrix metalloproteinases (MMP) and their endogenous tissue inhibitors of matrix metalloproteinases (TIMP), it remains unclear whether hypoxia can affect the migration of dendritic cells (DC). In this study, we showed that human monocyte-derived DC under hypoxic conditions in a transwell system have significantly reduced migratory capacity compared to normoxic controls. A moderate phenotypic change of hypoxic DC was observed. In hypoxic DC, we detected a twofold increase in TIMP-1 transcript levels, and downregulated expression of MMP-9 and membrane type 1-MMP genes by threefold and 17-fold, respectively. Our results suggest that hypoxia may inhibit DC migratory activity by regulating the balance between MMP and TIMP gene expression.
Qu
Xun
X
Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, China.
Yang
Mei-Xiang
MX
Kong
Bei-Hua
BH
Qi
Lan
L
Lam
Queenie Lai Kwan
QL
Yan
Shi
S
Li
Peng
P
Zhang
Min
M
Lu
Liwei
L
D002454:Cell Differentiation; D015687:Cell Hypoxia / Q000502:physiology*; D002465:Cell Movement; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D009000:Monocytes / Q000166:cytology*; D010641:Phenotype