Hypoxia regulates inflammatory gene expression in endothelial cells.
Hypoxia can activate the endothelium toward a pro-inflammatory phenotype and enhance leukocyte adhesion. This process is involved in pathological conditions such as vascular remodeling or ischemia-reperfusion injury. This study was aimed to obtain a global picture of the response of the endothelial cells to hypoxia with respect to inflammatory genes. To this purpose, we used a low density DNA microarray specifically designed to quantitate the expression of genes involved in the inflammatory pathways and a customized real-time PCR array. The expression of several pro-inflammatory genes known to be NF-kB target genes was decreased after the incubation of endothelial cells under hypoxia. In parallel, a decrease in the DNA binding activity of this transcription factor was observed. On the other hand, HIF-1 DNA binding activity was increased as well as the expression of several genes known to be regulated by this factor. Among them are several pro-inflammatory genes whose overexpression could account for the increase in leukocyte adhesion to the hypoxic endothelial cells. We concluded that hypoxia does not shift the endothelial cell phenotype to a more pro-inflammatory one probably because of a decrease in the expression of several cytokines. On the other hand, a clear response to hypoxia was observed with HIF-1 probably playing an important role in this process.
Flamant
Lionel
L
Laboratory of Biochemistry and Cellular Biology (URBC), FUNDP-University of Namur, 61 rue de Bruxelles, 5000 Namur, Belgium.
Toffoli
Sébastien
S
Raes
Martine
M
Michiels
Carine
C
D002448:Cell Adhesion; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism* / Q000502:physiology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D007249:Inflammation / Q000235:genetics*; D018836:Inflammation Mediators / Q000378:metabolism; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism; D007962:Leukocytes / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding
D051793:Hypoxia-Inducible Factor 1; D018836:Inflammation Mediators; D050856:Interferon Regulatory Factor-1; D016328:NF-kappa B; D004247:DNA